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Year 2 Medicine > Regulating Immunological Responses: Role of Cytokines and Chemokines > Flashcards

Regulating Immunological Responses: Role of Cytokines and Chemokines Flashcards

1
Q

Cytokines are … mediators

A

Cytokines are immune mediators

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2
Q

Concept of mediator or diffusible signalling molecule:

A

produced by a tissue or a cell and acting at a distance (from micrometres to several cm)

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3
Q

What is a soluble mediator?

A
  • Infection in lung - may get a fever due to adjustment of temperature setpoint - thermostat in hypothalamus in brain - bacteria does not travel to brain to give fever, but immune system responds to infection and produce cytokines (IL-1) is a pyrogen, gets to brain, causes fever
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4
Q

Define cytokine

A

any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.

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5
Q

Cell differentiation and haematopoiesis

A
  • These are the cytokines tha direct haematopoiesis along specific lineages. For instance, if there are high level of erythropoietin (EPO*) (as it happens if you go to high altitude that has lower oxygen) your stem cells will be directed mainly to become red blood cells (so you can use better the little oxygen you have). There are loads of cytokines here, the ones in bold – you should know and they may end up in an exam question.
  • *Abbreviations: IL-, interleukin; SCF, stem cell factor; G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor: EPO, erythropoietin; TPO, thrombopoietin (important ones in bold).
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6
Q

Cytokines to learn:

  • IL-, …
  • SCF, stem cell factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, …
  • TPO, thrombopoietin
A
  • IL-, interleukin
  • SCF, stem cell factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, erythropoietin
  • TPO, thrombopoietin
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7
Q

Cytokines to learn:

  • IL-, …
  • SCF, stem cell factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, erythropoietin
  • TPO, …
A
  • IL-, interleukin
  • SCF, stem cell factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, erythropoietin
  • TPO, thrombopoietin
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8
Q

Cytokines to learn:

  • IL-, Interleukin
  • SCF, … … factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, erythropoietin
  • TPO, …
A
  • IL-, Interleukin
  • SCF, stem cell factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, erythropoietin
  • TPO, thrombopoietin
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9
Q

Cytokines to learn:

  • IL-, Interleukin
  • SCF, stem cell factor
  • G- (GM)-CSF, … (granulocyte/macrophage) … … factor
  • EPO, Erythropoietin
  • TPO, thrombopoietin
A
  • IL-, Interleukin
  • SCF, stem cell factor
  • G- (GM)-CSF, granulocyte (granulocyte/macrophage) colony stimulating factor
  • EPO, erythropoietin
  • TPO, thrombopoietin
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10
Q

Mediators of host defense-1

  • Anti-viral mediators – Interferons, identified (1957) as products of virus-infected cells that interfere with viral replication
    • IFN-… (made by lymphocytes)
    • IFN-… (made by fibroblasts)
    • IFN-… (made by lymphocytes & NK cells) * IFN-… is, in fact, a very poor antiviral molecule - Don’t be mislead by the name
A
  • Anti-viral mediators – Interferons, identified (1957) as products of virus-infected cells that interfere with viral replication
    • IFN-alpha (made by lymphocytes)
    • IFN-beta (made by fibroblasts)
    • IFN-gamma (made by lymphocytes & NK cells) - * IFN-gamma is, in fact, a very poor antiviral molecule - Don’t be mislead by the name
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11
Q

Mediators of host defense-1

  • Anti-viral mediators – Interferons, identified (1957) as products of virus-infected cells that interfere with viral replication
    • IFN-alpha (made by …)
    • IFN-beta (made by …)
    • IFN-gamma (made by … & … cells) - IFN-gamma is, in fact, a very poor antiviral molecule - Don’t be mislead by the name
A
  • Anti-viral mediators – Interferons, identified (1957) as products of virus-infected cells that interfere with viral replication
    • IFN-alpha (made by lymphocytes)
    • IFN-beta (made by fibroblasts)
    • IFN-gamma (made by lymphocytes & NK cells) - * IFN-gamma is, in fact, a very poor antiviral molecule - Don’t be mislead by the name
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12
Q

Anti-viral mediators – …, identified (1957) as products of virus-infected cells that interfere with viral replication

A

Anti-viral mediators – Interferons, identified (1957) as products of virus-infected cells that interfere with viral replication

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13
Q

Mechanism of antiviral action of interferons

  • Main inteferons are IFN-alpha and IFN-beta
  • Interferon induces enzyme … - activate normally inactive ribonuclease - when active, degrades viral RNA
    • This is how it inhibits viral …
A
  • Main inteferons are IFN-alpha and IFN-beta
  • Interferon induces enzyme oligoadenylate synthetase 1 - activate normally inactive ribonuclease - when active, degrades viral RNA
    • This is how it inhibits viral replication
  • (2′,5′-oligoadenylate synthetase 1 (OAS1) is expressed at low constitutive levels and is upregulated by type I interferons (IFNs) via the ISRE, IFN-stimulated response element.. OAS1 protein accumulates in the cell cytoplasm as an inactive monomer. Following activation by viral double-stranded RNA (dsRNA), the enzyme oligomerizes to form a tetramer that synthesizes 2′,5′-oligoadenylates that, in turn, activate the constitutively expressed inactive ribonuclease L (RNaseL). The binding of 2′,5′-oligoadenylates to RNaseL triggers the dimerization of enzyme monomers and this then enables RNAseL to cleave cellular (and viral) RNAs)
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14
Q

Mediators of host defense-2

  • Immune activators:
    • Lymphocyte-activating cytokines (…-1)
    • T cell growth factors (…-2, -7, -9, -15; they share a co-receptor)
    • Macrophage-activating cytokines (IFN-gamma)
  • Cytotoxins: identified as products of activated lymphocytes or macrophages that can kill tumor cells
    • Tumor necrosis factor; TNF, also known as TNF-alpha - * TNF is, in fact, a very poor antitumor molecule - Don’t be mislead by the name
A
  • Immune activators:
    • Lymphocyte-activating cytokines (IL-1)
    • T cell growth factors (IL-2, -7, -9, -15; they share a co-receptor)
    • Macrophage-activating cytokines (IFN-gamma)•
  • Cytotoxins: identified as products of activated lymphocytes or macrophages that can kill tumor cells
    • Tumor necrosis factor; TNF, also known as TNF-alpha - * TNF is, in fact, a very poor antitumor molecule - Don’t be mislead by the name
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15
Q

Mediators of host defense-2

  • Immune activators:
    • …-activating cytokines (IL-1)
    • T cell growth factors (IL-2, -7, -9, -15; they share a co-receptor)
    • Macrophage-activating cytokines (IFN-…)
  • C…: identified as products of activated lymphocytes or macrophages that can kill tumor cells
    • … … factor; TNF, also known as TNF-alpha - * TNF is, in fact, a very poor antitumor molecule - Don’t be mislead by the name
A
  • Immune activators:
    • Lymphocyte-activating cytokines (IL-1)
    • T cell growth factors (IL-2, -7, -9, -15; they share a co-receptor)
    • Macrophage-activating cytokines (IFN-gamma)•
  • Cytotoxins: identified as products of activated lymphocytes or macrophages that can kill tumor cells
    • Tumor necrosis factor; TNF, also known as TNF-alpha - * TNF is, in fact, a very poor antitumor molecule - Don’t be mislead by the name
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16
Q

But the cytokine “baby boom” was in the 1980 with the identification of …-1, …-2 and TNF.

A

But the cytokine “baby boom” was in the 1980 with the identification of IL-1, IL-2 and TNF.

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17
Q
  • In the 1980s … was cloned and produced with the hope it would be an anticancer agent. However, it turned out to be too toxic
  • Same story for …-1, as a lymphocyte activator tested in AIDS
A
  • In the 1980s TNF was cloned and produced with the hope it would be an anticancer agent. However, it turned out to be too toxic
  • Same story for IL-1, as a lymphocyte activator tested in AIDS
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18
Q

Demonstration of the importance of cytokines in immunity: Immune-stimulating cytokine deficiency cause immunosuppression

  • Example: X-linked … (… … immunodeficiency) is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling component of the IL-2, IL-4 and IL-7 receptors (
A
  • X-linked SCID (severe combined immunodeficiency) is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling component of the IL-2, IL-4 and IL-7 receptors (This is just one example of how the lack of response to cytokines (in the slide, due to the lack of a common coreceptor) can cause severe immunodeficiecy (pictured: a «bubble baby»; this is not cured with bone marrow transplantation)
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19
Q

…-linked SCID (severe combined immunodeficiency) is caused by the genetic … (by …) of one receptor that is a common signalling component of the IL-2, IL-4 and IL-7 receptors

A

X-linked SCID (severe combined immunodeficiency) is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling component of the IL-2, IL-4 and IL-7 receptors - This is just one example of how the lack of response to cytokines (in the slide, due to the lack of a common coreceptor) can cause severe immunodeficiecy (pictured: a «bubble baby»; this is not cured with bone marrow transplantation)

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20
Q

X-linked SCID (… … …) is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling component of the IL-.., IL-.. and IL-.. receptors

A

X-linked SCID (severe combined immunodeficiency) is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling component of the IL-2, IL-4 and IL-7 receptors - This is just one example of how the lack of response to cytokines (in the slide, due to the lack of a common coreceptor) can cause severe immunodeficiecy (pictured: a «bubble baby»; this is not cured with bone marrow transplantation)

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21
Q

Cytokines in inflammation

  • The inflammatory role of (some) cytokines (inflammatory cytokines) was discovered by studying the immunopathogenesis of … during infection
  • Anthony Cerami (Rockefeller University) found that activated … produce an inflammatory mediator (cytokine) that, among other things, induced …
  • When they had its sequence, they found it was identical to TNF
  • This led to the finding that TNF is an inflammatory mediator
A
  • The inflammatory role of (some) cytokines (inflammatory cytokines) was discovered by studying the immunopathogenesis of cachexia during infection
  • Anthony Cerami (Rockefeller University) found that activated macrophages produce an inflammatory mediator (cytokine) that, among other things, induced cachexia.
  • When they had its sequence, they found it was identical to TNF
  • This led to the finding that TNF is an inflammatory mediator
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22
Q

Cytokines in inflammation

  • The inflammatory role of (some) cytokines (inflammatory cytokines) was discovered by studying the immunopathogenesis of cachexia during infection
  • Anthony Cerami (Rockefeller University) found that activated macrophages produce an inflammatory mediator (cytokine) that, among other things, induced cachexia.
  • When they had its sequence, they found it was identical to …
  • This led to the finding that … is an inflammatory mediator
A
  • The inflammatory role of (some) cytokines (inflammatory cytokines) was discovered by studying the immunopathogenesis of cachexia during infection
  • Anthony Cerami (Rockefeller University) found that activated macrophages produce an inflammatory mediator (cytokine) that, among other things, induced cachexia.
  • When they had its sequence, they found it was identical to TNF
  • This led to the finding that TNF is an inflammatory mediator
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23
Q

Cytokines in inflammation (2)

  • The cardinal signs of inflammation
    • …
    • …
    • redness
    • pain
    • tissue damage
  • Most of these can be explained by the biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the … endothelium, or through production of prostaglandins or chemokines.
A
  • The cardinal signs of inflammation
    • heat
    • swelling
    • redness
    • pain
    • tissue damage
  • Most of these can be explained by the biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the vascular endothelium, or through production of prostaglandins or chemokines.
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24
Q

Cytokines in inflammation (2)

  • The cardinal signs of inflammation
    • heat
    • swelling
    • redness
    • pain
    • tissue damage
  • Most of these can be explained by the biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the vascular endothelium, or through production of prostaglandins or chemokines.
A
  • The cardinal signs of inflammation
    • heat
    • swelling
    • redness
    • pain
    • tissue damage
  • Most of these can be explained by the biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the vascular endothelium, or through production of prostaglandins or chemokines.
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25
Q

Cytokines in inflammation (2)

  • The cardinal signs of inflammation
    • heat
    • swelling
    • redness
    • pain
    • tissue damage
  • Most of these can be explained by the biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the vascular endothelium, or through production of … or …
A
  • The cardinal signs of inflammation
    • heat
    • swelling
    • redness
    • pain
    • tissue damage
  • Most of these can be explained by the biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the vascular endothelium, or through production of prostaglandins or chemokines.
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26
Q

Inflammation

  • Macrophages encountering bacteria in the tissues are triggered to release … that increase the … of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce … that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
A
  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
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27
Q

Inflammation

  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass … the tissues.
  • They also produce chemokines that direct the migration of … to the site of infection.
  • The … of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
A
  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
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28
Q

Inflammation

  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells … to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The … of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
A
  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
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29
Q

Inflammation

  • … encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then … are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
A
  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
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30
Q

Inflammation

  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the r.., s.., h.., and p.., known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
A
  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
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31
Q

Inflammation

  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated … may also contribute to inflammation.
A
  • Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
  • They also produce chemokines that direct the migration of neutrophils to the site of infection.
  • The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.
  • The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells.
  • Later in an immune response, activated lymphocytes may also contribute to inflammation.
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32
Q

… and … are the principal inflammatory cells

A

Neutrophils and macrophages are the principal inflammatory cells (Later in an immune response, activated lymphocytes may also contribute to inflammation)

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33
Q

There are many TNF-mediated diseases

  • 1-… shock
  • 2-Multiple … …
  • 3-Respiratory … syndrome
  • 4-Rheumatoid arthritis*
  • 5-Inflammatory bowel disease*
  • 6-Graft-versus-host rejection
  • 7-Diabetes
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
A
  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-Respiratory distress syndrome
  • 4-Rheumatoid arthritis
  • 5-Inflammatory bowel disease
  • 6-Graft-versus-host rejection
  • 7-Diabetes
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
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34
Q

There are many TNF-mediated diseases

  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-Respiratory distress syndrome
  • 4-… arthritis*
  • 5-… … disease*
  • 6-Graft-versus-host rejection
  • 7-Diabetes
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
A
  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-Respiratory distress syndrome
  • 4-Rheumatoid arthritis
  • 5-Inflammatory bowel disease
  • 6-Graft-versus-host rejection
  • 7-Diabetes
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
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35
Q

There are many TNF-mediated diseases

  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-Respiratory distress syndrome
  • 4-Rheumatoid arthritis*
  • 5-Inflammatory bowel disease*
  • 6-…-versus-host rejection
  • 7-Diabetes
  • 8-… fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
A
  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-Respiratory distress syndrome
  • 4-Rheumatoid arthritis*
  • 5-Inflammatory bowel disease*
  • 6-Graft-versus-host rejection
  • 7-Diabetes
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
36
Q

There are many TNF-mediated diseases

  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-… distress syndrome
  • 4-Rheumatoid arthritis*
  • 5-Inflammatory bowel disease*
  • 6-Graft-versus-host rejection
  • 7-D..
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
A
  • 1-Septic shock
  • 2-Multiple organ failure
  • 3-Respiratory distress syndrome
  • 4-Rheumatoid arthritis*
  • 5-Inflammatory bowel disease*
  • 6-Graft-versus-host rejection
  • 7-Diabetes
  • 8-Pulmonary fibrosis
  • *red - where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models
37
Q

Cytokines in allergy

  • While Th1 cytokines are important in inflammatory diseases, Th… cytokines are important in allergic diseases
A
  • While Th1 cytokines are important in inflammatory diseases, Th2 cytokines are important in allergic diseases
38
Q

While Th1 cytokines are important in … diseases, Th2 cytokines are important in … diseases

A

While Th1 cytokines are important in inflammatory diseases, Th2 cytokines are important in allergic diseases (This is just to say that there is no «Th2=good cytokine» and «Th1=bad cytokine». Th2 are «good» in inflammation but «bad» in allergic disease)

39
Q

T lymphocytes expressing … are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2-type cytokines.

A

T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2-type cytokines.

40
Q

T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into … and …

A

T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2-type cytokines.

41
Q
  • Th… cells help macrophage activation - chemokines,cytokines etc produced - pro-inflammatory
  • Th… cells activate eosinophil and IgE activation - cytokines produced by Th2 cells are anti-inflammatory
A
  • Th1 cells help macrophage activation - chemokines,cytokines etc produced - pro-inflammatory
  • Th2 cells activate eosinophil and IgE activation - cytokines produced by Th2 cells are anti-inflammatory
42
Q
  • Th1 cells help … activation - chemokines,cytokines etc produced - pro-inflammatory
  • Th2 cells activate … and Ig… activation - cytokines produced by Th2 cells are anti-inflammatory
A
  • Th1 cells help macrophage activation - chemokines,cytokines etc produced - pro-inflammatory
  • Th2 cells activate eosinophil and IgE activation - cytokines produced by Th2 cells are anti-inflammatory
43
Q
  • Th1 cells help macrophage activation - chemokines,cytokines etc produced - …-inflammatory
  • Th2 cells activate eosinophil and IgE activation - cytokines produced by Th2 cells are …-inflammatory
A
  • Th1 cells help macrophage activation - chemokines,cytokines etc produced - pro-inflammatory
  • Th2 cells activate eosinophil and IgE activation - cytokines produced by Th2 cells are anti-inflammatory
44
Q

T cell subsets

  • Fill in the blanks - are they inflammatory, anti-inflammatory, allergy?
A

This slide is a bit oversimplified but highlights the MAIN role of each subset of helper T cells (Th) in the context of disease

45
Q

T cell subsets

  • Fill in the blanks - are they inflammatory, anti-inflammatory, allergy?
A

This slide is a bit oversimplified but highlights the MAIN role of each subset of helper T cells (Th) in the context of disease

46
Q

Chemokines (chemotactic cytokines)

  • Chemotaxis (… towards a gradient):
  • Discovered originally for the ability of … to chase bacteria
  • Then to explain … of leukocytes (macrophages, PMN to the site of infection and inflammation; in inflammation they cause tissue damage)
  • Important in the homing and migration of cells of the immune system (= role in development)
A
  • Chemotaxis (migration towards a gradient):
  • Discovered originally for the ability of neutrophils to chase bacteria
  • Then to explain infiltration of leukocytes (macrophages, PMN to the site of infection and inflammation; in inflammation they cause tissue damage)
  • Important in the homing and migration of cells of the immune system (= role in development)
47
Q

Chemokines (chemotactic cytokines)

  • … (migration towards a gradient):
  • Discovered originally for the ability of neutrophils to chase bacteria
  • Then to explain infiltration of … (macrophages, PMN to the site of infection and inflammation; in inflammation they cause tissue damage)
  • Important in the homing and migration of cells of the immune system (= role in …)
A
  • Chemotaxis (migration towards a gradient):
  • Discovered originally for the ability of neutrophils to chase bacteria
  • Then to explain infiltration of leukocytes (macrophages, PMN to the site of infection and inflammation; in inflammation they cause tissue damage)
  • Important in the homing and migration of cells of the immune system (= role in development)
48
Q

Chemokines (chemotactic cytokines)

  • Chemotaxis (migration towards a …):
  • Discovered originally for the ability of neutrophils to chase bacteria
  • Then to explain infiltration of leukocytes (macrophages, PMN to the site of infection and …; in … they cause tissue damage)
  • Important in the homing and migration of cells of the immune system (= role in development)
A
  • Chemotaxis (migration towards a gradient):
  • Discovered originally for the ability of neutrophils to chase bacteria
  • Then to explain infiltration of leukocytes (macrophages, PMN to the site of infection and inflammation; in inflammation they cause tissue damage)
  • Important in the homing and migration of cells of the immune system (= role in development)
49
Q

Chemokines to remember!!

  • MCP, monocyte chemotactic protein - attract …
  • IL-8, interleukin-8 - attract …
A
  • MCP, monocyte chemotactic protein - attract monocytes
  • IL-8, interleukin-8 - attract neutrophils
50
Q

Chemokines to remember!!

  • …, … … protein - attract monocytes
  • … - attract neutrophils
A
  • MCP, monocyte chemotactic protein - attract monocytes
  • IL-8, interleukin-8 - attract neutrophils
51
Q

Chemokines Overview

A

Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues. They also produce chemokines that direct the migration of neutrophils to the site of infection. The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel. The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells. Later in an immune response, activated lymphocytes may also contribute to inflammation.

52
Q

Therapeutic use: recapitulates the various roles of cytokines

  • IFN-gamma … activation
  • IFN-beta (MS) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
A
  • IFN-gamma Macrophage activation
  • IFN-beta (MS) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
53
Q

Therapeutic use: recapitulates the various roles of cytokines

  • IFN-gamma Macrophage activation
  • IFN-beta (MS) “…modulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
A
  • IFN-gamma Macrophage activation
  • IFN-beta (MS) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
54
Q

Therapeutic use: recapitulates the various roles of cytokines

  • IFN-gamma Macrophage activation
  • IFN-beta (in … disease) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-… (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
A
  • IFN-gamma Macrophage activation
  • IFN-beta (MS) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
55
Q

Therapeutic use: recapitulates the various roles of cytokines

  • IFN-gamma Macrophage activation
  • IFN-beta (MS) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
A
  • IFN-gamma Macrophage activation
  • IFN-beta (MS) “immunomodulation”
  • Host defense
    • IL-2 (melanoma, renal cell carcinoma)
    • IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)
  • Hemopoiesis
    • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
    • G-CSF (chemotherapy-induced neutropenia)
    • IL-11 (thrombocytopenia in oncology)
    • EPO (anaemia)
56
Q

IFN-γ is one of the most important mediators of immunity and inflammation and plays a key role in … activation

A

IFN-γ is one of the most important mediators of immunity and inflammation and plays a key role in macrophage activation

57
Q

IFN-β therapy was one the first approved therapy for …

A

IFN-β therapy was one the first approved therapy for MS

58
Q

Role of Cytokines in Host Defence

  • IL-… has been approved for use of (melanoma, renal cell carcinoma) - not used much though
  • IFN-alpha is used as anti viral agent - viral hepatitis, also hairy cell leukemia, kaposi
A
  • IL-2 has been approved for use of (melanoma, renal cell carcinoma) - not used much though
  • IFN-alpha is used as anti viral agent - viral hepatitis, also hairy cell leukemia, kaposi
59
Q

Role of Cytokines in Host Defence

  • IL-2 has been approved for use of (…, … cell …) - not used much though
  • IFN-alpha is used as anti viral agent - viral hepatitis, also hairy cell leukemia, kaposi
A
  • IL-2 has been approved for use of (melanoma, renal cell carcinoma) - not used much though
  • IFN-alpha is used as anti viral agent - viral hepatitis, also hairy cell leukemia, kaposi
60
Q

Role of Cytokines in Host Defence

  • IL-2 has been approved for use of (melanoma, renal cell carcinoma) - not used much though
  • IFN-… is used as anti viral agent - viral hepatitis, also hairy cell leukemia, kaposi
A
  • IL-2 has been approved for use of (melanoma, renal cell carcinoma) - not used much though
  • IFN-alpha is used as anti viral agent - viral hepatitis, also hairy cell leukemia, kaposi
61
Q

Interferon …-2b is the form of the drug that works against chronic viral hepatitis B infection.

A

Interferon alpha-2b is the form of the drug that works against chronic viral hepatitis B infection.

62
Q

Hemopoiesis - Cytokines

  • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced …)
  • IL-… (thrombocytopenia in oncology)
  • EPO (anaemia)
A
  • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • EPO (anaemia)
63
Q

Hemopoiesis - Cytokines

  • GM-CSF (myeloreconstitution following … … transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • EPO (…)
A
  • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • EPO (anaemia)
64
Q

Hemopoiesis - Cytokines

  • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-… (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • … (anaemia)
A
  • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • EPO (anaemia)
65
Q

Hemopoiesis - Cytokines

  • GM-… (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • EPO (anaemia)
A
  • GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
  • G-CSF (chemotherapy-induced neutropenia)
  • IL-11 (thrombocytopenia in oncology)
  • EPO (anaemia)
66
Q

For …-induced …, G-CSF is administered until there is >1000 neutrophils/µl.

A

For chemotherapy-induced neutropenia, G-CSF is administered until there is >1000 neutrophils/µl.

67
Q

EPO is used to treat …

A

EPO is used to treat anaemia

68
Q

Could IFN be a treatment for Covid-19 (viral infection)?

A

Current clinical trials for treatment of Covid-19

69
Q

Therapeutic use - Cytokine Inhibition in Inflammation

  • Anti-… and … (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (… arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
A
  • Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
70
Q

Therapeutic use - Cytokine Inhibition in Inflammation

  • Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-… (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (…, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
A
  • Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
71
Q

Therapeutic use - Cytokine Inhibition in Inflammation

  • Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-… (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-… (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
A
  • Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
72
Q

Therapeutic use - Cytokine Inhibition in Inflammation

  • Anti-TNF and sTNFR (R.A., …, ulcerative colitis, psoriasis)
  • IL-1Ra (… arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
A
  • Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
  • IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
  • Anti-IL-6, IL-6R (rheumatoid arthritis),
  • Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)
  • Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
  • Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)
73
Q

Could anti-IL-6 be a treatment for Covid-19 (pathogenesis)?

74
Q

Cytokine Inhibition

  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) … to the cytokine (middle)
    • 2) … to their … so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
A
  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) antibody to the cytokine (middle)
    • 2) antibody to their receptors so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
75
Q

Cytokine Inhibition

  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) antibody to the cytokine (middle)
    • 2) antibody to their receptors so that the cytokine can’t … anymore (left)
    • 3) … (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
A
  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) antibody to the cytokine (middle)
    • 2) antibody to their receptors so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
76
Q

Cytokine Inhibition

  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) antibody to the cytokine (middle)
    • 2) antibody to their … so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus … with the membrane receptor
A
  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) antibody to the cytokine (middle)
    • 2) antibody to their receptors so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
77
Q

Cytokine Inhibition

  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) … to the cytokine (middle)
    • 2) … to their receptors so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
A
  • Ths slide summarizes the three main approachers to block cytokines:
    • 1) antibody to the cytokine (middle)
    • 2) antibody to their receptors so that the cytokine can’t bind anymore (left)
    • 3) soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor
78
Q

Cytokine Inhibition - Approved Drugs

  • block cytokines: 1) antibody to the cytokine
    • Anti-IL-1beta (canakinumab)
    • Anti-IL-… (siltuximab)
    • Anti-IL-… (ixekinumab, secukinumab)
A
  • Anti-IL-1beta (canakinumab)
  • Anti-IL-6 (siltuximab)
  • Anti-IL-17 (ixekinumab, secukinumab)
79
Q

Cytokine Inhibition - Approved Drugs

  • block cytokines: 1) … to the …
    • Anti-IL-1beta (canakinumab)
    • Anti-IL-6 (siltuximab)
    • Anti-IL-17 (ixekinumab, secukinumab)
A
  • block cytokines: 1) antibody to the cytokine
    • Anti-IL-1beta (canakinumab)
    • Anti-IL-6 (siltuximab)
    • Anti-IL-17 (ixekinumab, secukinumab)
80
Q

Cytokine Inhibition - Approved Drugs

  • antibody to their … so that the … can’t bind anymore
    • Anti-… (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
A
  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-TNF (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
81
Q

Cytokine Inhibition - Approved Drugs

  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-TNF (infliximab, adalimumab…)
    • Anti-IL-… (rilonacept)
    • Anti-IL-… (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
A
  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-TNF (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
82
Q

Cytokine Inhibition - Approved Drugs

  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-TNF (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-…R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
A
  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-TNF (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
83
Q

Cytokine Inhibition - Approved Drugs

  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-… (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
A
  • antibody to their receptors so that the cytokine can’t bind anymore
    • Anti-TNF (infliximab, adalimumab…)
    • Anti-IL-1R (rilonacept)
    • Anti-IL-6R (tocilizumab, sarilumab…)
    • Anti-IL-17R (brodalumab)
    • Anti-IL-12/IL-23 (ustekinumab, briakinumab)
84
Q

Cytokine Inhibition - Approved Drugs

  • soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor.
    • Soluble… (etanercept)
A
  • soluble (decoy) receptors that bind the cytokine (because they are receptors) but, not being on the membrane, do not signal and thus compete with the membrane receptor.
    • SolubleTNFR (etanercept)
85
Q

Protein Inhibitor of Cytokines (not antibody)

  • IL-… antagonist (Anakinra)
  • Bind to the cytokine receptor but not signal - receptor antagonist blocks IL-… activity
A
  • IL-1R antagonist (Anakinra)
  • Bind to the cytokine receptor but not signal - receptor antagonist blocks IL-1 activity
86
Q

Meaning of the term “…” (from the Greek pleion = more): acts on many different targets (has many actions)

A

Meaning of the term “pleiotropic” (from the Greek pleion = more): acts on many different targets (has many actions)

87
Q

The “Cytokine Storm” in Covid-19

  • Summary of cytokines involved
A
  • Summary of cytokines involved

Year 2 Medicine (162 decks)

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