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PHARM 321 > Cytokines as Therapeutics > Flashcards

Cytokines as Therapeutics Flashcards

1
Q

IL-2 role

A

T-cell growth factor
Binds IL-2 receptor on lymphocytes
Pro-inflammatory cytokine
Secreted by CD4 lymphocytes; expansion and proliferation of lymphoid cells (B-cells, NK cells); induce secretion of other pro-inflammatory cytokines (e.g., TNF) and immunoglobulins

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2
Q

Main physiological roles of IL-2

A

Anti-viral/anti-bacterial immune response, select regulatory T-cells, suppress self anti-self recognition
Both immunostimulatory and immunosuppressive effects

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3
Q

Therapeutic uses for IL-2

A

Metastatic renal carcinoma, acute myeloid leukemia

Limited overall use due to toxicity (auto-immune disorders, capillary leak syndrome, cardiac, CNS, renal/liver toxicity

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4
Q

Main function of interferons

A

Interfere with viral replication

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5
Q

Type I and Type II interferoms

A

Type I = INF-alpha, INF-beta

Type II = INF-gamma

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6
Q

Immunostimulatory and immunosuppressive functions of Type I INF

A

Immunostimulatory: Promote Th1 repsonse, induce IL-15 secretion (promote differentiation of NK cells memory T-cells); induce INF-gamma secretion; induce chemokine secretion
Immunosuppressive: Increase IL-10, decrease IL-12 (pro-inflammatory cytokine)

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7
Q

Type II INF immunostimulatory functions

A

Activate APCs, increase proliferation of other cells involved in Th1 response

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8
Q

Therapeutic INF uses?

A

Treat infectious diseases, cancer, autoimmune disease (hep. B and C; hairy cell leukaemia)
Can also precipitate autoimmune diseases

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9
Q

INF-alpha2a indications

A

Acute and chronic hep C, chronic hep B, leukemias, lymphona

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10
Q

INF-alpha2a mechanism of action

A

Decreases cell proliferation and differentiation; decrease replication of virally infected cells

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11
Q

Major adverse effects of INF-alpha2a

A

Immunosuppression, myelosuppression, auto-immune diseases, headache, fatigue, fever

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12
Q

Advantages of a PEGylated formulation of cytokine therapeutics?

A

Longer half-life

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13
Q

Indications and mechanism of action of INF-alpha2b?

A

Same as INF-alpha2a

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14
Q

Major adverse effects of INF-alpha2b?

A 
Allergic and hypersensitivity reactions
Chest pain
Fatigue, fever
Headache
Myelosuppression
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15
Q

INF-beta indication?

A

Relapsing MS

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16
Q

Mechanism of action of INF-beta?

A

Anti-viral and immunoregulatory properties; action in MS not fully understood

17
Q

Major adverse effects of INF-beta?

A

Cardiovascular issues (HTN, tachycardia), myelosuppression, allergy/hypersensitivity

18
Q

G-CSF and GM-CSF indications

A

Neutropenia (decreased neutrophils - chemo, AIDS, bone marrow transplant), harvesting of peripheral blood cells

19
Q

Mechanism of action of G-CSF and GM-CSF

A

Bind receptors (CD114, CD116), stimulate granulocytes and macrophage proliferation

20
Q

Common adverse effects of G-CSF and GM-CSF?

A

Nausea, vomiting (questionable), bone pain, allergy, hypersensitivity

21
Q

What is erythropoietin?

A

Type of colony stimulating factor - stimulates RBC production

22
Q

Indications for erythropoietin?

A

Anemia (from chemo or chronic renal failure)

23
Q

Mechanism of action of erythropoietin?

A

Bind erythropoietin receptor, stimulate erythroid cells (RBCs) proliferation

24
Q

Major adverse effects of erythropoietin?

A

Pure RBC aplasia, thickened blood due to increase RBCs (CHF, MI, DVT, pulmonary embolism, stroke), seizures

25
Q

Anti-cytokine therapy?

A

Inhibit pro-inflammatory cytokines (e.g., TNF) by binding cytokine/cytokine receptor
Anti-TNF, anti-IL-2, etc.

26
Q

Etanercept

A 
Fusion protein (soluble portion of TNF receptor linked to Fc portion of immunoglobulin)
Binds circulating TNF, decreases its serum concentration
27
Q

Infliximab and adalimumab

A

Binds circulating TNF-alpha, decreases its concentration

28
Q

Daclizumab

A

Binds IL-2 receptor on activated lymphocytes, prevents binding of IL-2

29
Q

Basiliximab

A

Binds IL-2 receptor and blocks IL-2 from binding

PHARM 321 (9 decks)

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