Cytokines and Chemokines Flashcards
Cytokines and Chemokines
Signalling proteins
Functions of cytokines and chemokines
- They enable cross-talk between the components of immune system
- They drive immune cellular movement and action
Clinically relevant cytokines and chemokines
- IL-1 (Interleukin-1)
- IL-2
- IL-6
- IL-10
- IL-17
- TNF (Tumour necrosis factor)
- IFN (interferon)
IL-1: secreted by- ?
TNF is released by- ?
Co-stimulator(s) of T cell roliferation
Co-stimulator of B cell proliferation
IL-1: Functions on endothelium
IL-1: Functions on endothelium
IL-1: increases endothelial release of - ?
IL-1: Effect on vessels ?
IL-1: How does it cause vasodialation or increase vascular permeability ?
IL-1: Role in sepsis ?
3 Cytokines that act on hypothalamus to cause pyrexia
IL-1: Clinical significance
- Upregulated in many ‘autoinflammatory disease’, e.g. Periodic fever syndromes
- It can be blocked by ‘Anakinra’
- Anakinra is an effective treatment for periodic fever syndrome
IL-2: Functions
Drives T cell proliferation
IL-2: Clinical significance
- Upregulated in ‘T-cell driven diseases’, e.g. Transplant rejection
- It can be supressed by calcinurin inhibitors (ciclosporin and tacrolimus)
- Ciclosporin and Tacrolimus (Calcinurin inhibitors) are effective treatment of transplant rejection
IL-6: Function
- Pro-inflammatory cytokine
- Key driver in acute phase response (especially CRP production)
IL-6: Clinical significance
- Upregulated in rheumatoid arthritis (RA) & other acute phase responses
- It is inhibited by tocilizumab
- Tocilizumab is an effective treatment of rheumatoid arthritis
CRP monitoring in a patient who is on ‘tocilizumab’ treatment
Patients are unable to mount a CRP response (even during infection)
Normal CRP would not be reassuring in this setting
IL-10: Function
- Anti-inflammatory cytokine
- Downregulates other cytokine production
- Supressed HLA class II expression
IL-10: Clinical significance
- NOT much really clinically significant
- BUT one of the few “truly anti-inflammatory cytokines”
IL-17: Function
- Stimulates production of Th17 cells
IL-17: Clinical significance
Not yet
But as Th17 is a very recent discovery >>> manipulation of this pathway is likely to become very important in the coming years
TNF: Function
- Pro-inflammatory cytokine
- Recruits T cells
- Central to granuloma formation
TNF: Source
Produced by “macrophages” >>> to recruit T Cells
TNF: Clinical significance
- Upregulated in rheumatoid arthritis
- It is inhibited by ‘Adalimumab’
- Adalimumab is a mainstay therapy in rheumatoid arthritis
Side-effect of ‘Adalimumab’
Reactivation of granulomatous disease
IFN: Function
- Pro-inflammatory cytokine
- Important in response to “viral infection”
IFN: Clinical significance
-
Use as a treatment of >>
- Chronic viral infection (hepatitis C)
- Multiple sclerosis (MS)
Side-effects of IFN (Interferon)
Flu-like symptoms
Which cytokines do they inhibit?
- Anakinra-?
- Ciclosporin (Calcinurin inhibitor)-?
- Tacrolimus (Calcinurin inhibitor)-?
- Tocilizumab-?
- Adalimumab-?
- Anakinra >> IL-1
- Ciclosporin (Calcinurin inhibitor) >> IL-2
- Tacrolimus (Calcinurin inhibitor) >> IL-2
- Tocilizumab >> IL-6
- Adalimumab >> TNF
Which diseases do they treat?
- Anakinra-?
- Ciclosporin (Calcinurin inhibitor)-?
- Tacrolimus (Calcinurin inhibitor)-?
- Tocilizumab-?
- Adalimumab-?
- IFN-?
- Anakinra >>> Periodic fever syndrome
- Ciclosporin (Calcinurin inhibitor) >>> Transplant rejection
- Tacrolimus (Calcinurin inhibitor) >>> Transplant rejection
- Tocilizumab >>> Rheumatoid arthritis
- Adalimumab >>> Rheumatoid arthritis
- IFN >>> Chronic infection (hepatitisC), Multiple sclerosis
Important side effects of the following >>>
- Tocilizumab-?
- Adalimumab-?
- IFN-?
- Tocilizumab >>> unable to mount a CRP response
- Adalimumab >>> reactivation of TB & other granulomatous diseases
- IFN >>> Flu-like symptoms
Important pro-inflammatory cytokines
- IL-1
- IL-6
- TNF
- IFN
Name an important truly anti-inflammatory cytokine
IL-10
Which cytokine does downregulate other cytokine production?
IL-10
Which cytokine does supress HLA class II expression?
IL-10
Which cytokine has an important response to viral infection?
IFN (interferon)
Which cytokine is central to granuloma formation?
TNF (Tumour necrosis factor)
Which cytokine is a key driver of acute-phase response or mainly CRP production?
IL-6
Which cytokine does drive T-cell profileration?
Many of them
IL-2 mainly drives T-cell proliferation
Which cytokine does stimulate production of T17 cells?
IL-17
Subsets of T-helper cells
T cell type that is involved in ‘cell mediated immune response’ and ‘delayed type IV hypersensitivity’
Th1 secrets - ?
T cell type that is involved in ‘humoral (antibody-mediated) immunity’
T-cell type that is involved in type-1 hypersensitivity reaction
Th 2 cell secrets - ?
Subset of T-helper cells - that is related to IgE production
