Cytokines and chemokines

Question 1

Cytokines that mediate and regulate innate immunity

Answer 1

IL1, IL6, IL10, IL12
TNF alpha
INFa/b/gamma

MOA: act on endothelial cells and leukocytes to stimulate innate responses

Question 2

Cytokines that mediate and regulate adaptive immunity

Answer 2

IL2, IL4, IL5, TGFb

MOA: act on lymphocyte to stimulate and regulate adaptive response to antigen.

Question 3

Cytokines that stimulate haematopoesis

Answer 3

Stem cell factor, IL3, IL7, GM-CSF.

MOA: act on bone marrow to stimulate growth and differentiation of leukocytes and lymphocytes.

Question 4

Chemokines that control homeostasis

Answer 4

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

Question 5

Inflammatory chemokines

Answer 5

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.

Question 6

Angiogenic chemokines

Answer 6

CXCL1-14

Promote angiogenesis

Question 7

Cytokines produced by Th 1

Answer 7

IFN a/b
IL-1b
IL-6
TNF a

Question 8

Cytokines produced by Th1/Th17 which has effects in the adaptive response

Answer 8

IFN gamma
IL-17
IL-2
IL-12/23
TNFbeta

Question 9

Cytokines produced by Th2

Answer 9

IL4, IL5, IL10

Question 10

Anti inflammatory cytokines produced by T regs

Answer 10

IL 10

TGFb

Question 11

Function of TNFa

Answer 11

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.

Question 12

IL 1

Answer 12

leads to inflammation, promotes fever and sepsis.

Question 13

IL 2

Answer 13

Growth factor for activated T cells. CD28 dependent co stimulation of activate T cells induces expression of the high affinity IL-2 receptor.

Question 14

IL 6

Answer 14

Produced by T cells, macrophage, endothelial cell. Induces local and systemic inflammation and acute phase response.

Question 15

IL 12/IL 23

Answer 15

Dimeric molecule sharing one chain in common (P40). Produced by Th1 and Th17.

Question 16

IL 17

Answer 16

Mobilise and activate neutrophils.

Defect in this causes autoimmunity

Question 17

IL 10

Answer 17

Anti-inflammatory, attenuate production of inflamatory cytokine.

But not useful in controlling disease such as psoriatic arthritis, RA, UC.

Question 18

Examples of anti-TNFa

Answer 18

• infliximab
• centolizumab
• adalimumab
• golimumab

Question 19

Etanercept

Answer 19

TNF receptor fused to Fc portion of IgG -> becomes a competitive inhibitor

Question 20

Tozilizumab

Answer 20

mab agains IL6Ra.
Indication: RA and Juvenile RA
Giant cell arteritis

Question 21

Anakinra

Answer 21

human recombinant IL-1RA (antagonist)

PBS indication: CAPS

Indication:
Gout, RA, behcet’s, Ank Spond, Uveitis

Question 22

Basiliximab

Answer 22

blocks IL-2R on activated T cells.

Indication:

• prevent organ transplant rejection.
• GVHD
• uveitis

Question 23

p40 inhibitor

Answer 23

(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.

Question 24

Secukinumab

Answer 24

Inhibitory IL17A mab

Indication:
psoriasis, psoriatic arthropathy, Ank spond, ?MS

Question 25

Tofacitinib

Answer 25

JAK1 and JAK 3 inhibitor

Inhibit cytokine induced cell activation and thus inflammation.

Similar benefit in RA to adalimumab

Question 26

Fostamatinib

Answer 26

inhibit spleen tyrosine kinase which inhibit downstream synthesis of proinflammatory cytokine