Cytokines and chemokines Flashcards
Cytokines that mediate and regulate innate immunity
IL1, IL6, IL10, IL12
TNF alpha
INFa/b/gamma
MOA: act on endothelial cells and leukocytes to stimulate innate responses
Cytokines that mediate and regulate adaptive immunity
IL2, IL4, IL5, TGFb
MOA: act on lymphocyte to stimulate and regulate adaptive response to antigen.
Cytokines that stimulate haematopoesis
Stem cell factor, IL3, IL7, GM-CSF.
MOA: act on bone marrow to stimulate growth and differentiation of leukocytes and lymphocytes.
Chemokines that control homeostasis
CCL 14, 19, 20, 21, 25, 27, CXCL21, CXCL13
MOA; control the migration of cells during the normal development and maintenance of tissues and lymphoid organs
Inflammatory chemokines
CXCL8, CCL2,3,4,5, 11, CXCL10.
MOA: produced in response to infection or injury and direct migration of leukocytes into the infected or damaged cells.
Angiogenic chemokines
CXCL1-14
Promote angiogenesis
Cytokines produced by Th 1
IFN a/b
IL-1b
IL-6
TNF a
Cytokines produced by Th1/Th17 which has effects in the adaptive response
IFN gamma IL-17 IL-2 IL-12/23 TNFbeta
Cytokines produced by Th2
IL4, IL5, IL10
Anti inflammatory cytokines produced by T regs
IL 10
TGFb
Function of TNFa
Inflammatory cytokines produced by macrophages/monocytes during acute inflammation leading to diverse range of signalling within cells, leading to necrosis/apoptosis
Assoc. in: RA, Ank Spond, Psoriatic Arthritis, Juvenile idiopathic arthritis, UC, Chrons.
IL 1
leads to inflammation, promotes fever and sepsis.
IL 2
Growth factor for activated T cells. CD28 dependent co stimulation of activate T cells induces expression of the high affinity IL-2 receptor.
IL 6
Produced by T cells, macrophage, endothelial cell. Induces local and systemic inflammation and acute phase response.
IL 12/IL 23
Dimeric molecule sharing one chain in common (P40). Produced by Th1 and Th17.
IL 17
Mobilise and activate neutrophils.
Defect in this causes autoimmunity
IL 10
Anti-inflammatory, attenuate production of inflamatory cytokine.
But not useful in controlling disease such as psoriatic arthritis, RA, UC.
Examples of anti-TNFa
- infliximab
- centolizumab
- adalimumab
- golimumab
Etanercept
TNF receptor fused to Fc portion of IgG -> becomes a competitive inhibitor
Tozilizumab
mab agains IL6Ra.
Indication: RA and Juvenile RA
Giant cell arteritis
Anakinra
human recombinant IL-1RA (antagonist)
PBS indication: CAPS
Indication:
Gout, RA, behcet’s, Ank Spond, Uveitis
Basiliximab
blocks IL-2R on activated T cells.
Indication:
- prevent organ transplant rejection.
- GVHD
- uveitis
p40 inhibitor
(IL12/IL23)
Targeting p40 can attenuate both Th1 (driven by IL12) and Th17 (enhanced by IL23)
e. g. ustekinumab and briakinumab.
indication: chrons, psoriatic arthropathy, chronic plaque psoriasis.
ALso RA despite MTIX, refractory GCA, Takayasu arteritis, Ank spond, Behcet’s.
Secukinumab
Inhibitory IL17A mab
Indication:
psoriasis, psoriatic arthropathy, Ank spond, ?MS
Tofacitinib
JAK1 and JAK 3 inhibitor
Inhibit cytokine induced cell activation and thus inflammation.
Similar benefit in RA to adalimumab
Fostamatinib
inhibit spleen tyrosine kinase which inhibit downstream synthesis of proinflammatory cytokine