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Interleukins And Interferon-gamma: Receptors, Functions, And Roles In Diseases Boonthorn 8 April 2011

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Page 1: Interleukins and interferon gamma

Interleukins And Interferon-gamma: Receptors,Functions, And Roles In Diseases

Boonthorn

8 April 2011

Page 2: Interleukins and interferon gamma

INTERLEUKINS Secreted proteins that bind to their

specific receptors and play a role in the communication among leukocytes

Assigned to each family based on sequence homology and receptor chain similarities or functional properties

Action Pleiotropic effect Redundancy

Classification Type I cytokines (hematopoietin) Type II cytokines (interferon)

Page 3: Interleukins and interferon gamma

CLASSIFICATION Type I cytokines (contain WSXWS)

gp 130-utilizing : IL-6,IL-11,IL-27,IL-31β chain utilizing : IL-3,IL-5 chain utilizing : IL-2,IL-4,IL-7,IL-9,IL-15,IL-21Hetero-dimeric : IL-13,IL-12 subfamily(IL-12,IL-

23,IL-27,IL-35) Type II cytokines (not contain WSXWS)

Hetero-dimeric : IL-10 subfamily (IL-10,IL-19,20,22,24,26,IL-28,29,30),IFN-

IL-1/TLR : IL-1α/β,IL-18,IL-33,IL-37(IL-1F) IL-17 : IL-17A-D,F , IL-25(IL-17E)Receptor tyrosine kinase : IL-16,IL32,IL-34

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Cytokine signaling by Jak-Stat pathway. Cytokine-induced clustering of receptors leads to Jak-

mediated phosphorylation of the receptor chains, attachment of inactive stats, phosphorylation of

the bound stats (also by the jaks), dimerization of stats and migration to the nucleus, and stimulation

of gene transcription

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CLASSIFICATION TH2-like cytokines : IL-5,IL-13,IL-25,IL-31 ILs with chemokine activity : IL-8,IL-16

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Antigen presentation by DCs to naive T cells and other factors induces the T cells to produce ils and differentiate into TH1, TH2, TH9, TH17, TH22, or follicular TH (TFH) cells. These T-cell subsets can promote different types of inflammatory responses on the basis of their respective cytokine profiles, responses to chemokines, and interactions with other cells.

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 8: Interleukins and interferon gamma

The receptors of the IL-2 family( IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21). Receptors contain the common cytokine receptor γ chain (CD132, γc). IL-13R shares IL-4ra with IL-4, and TSLPR shares IL-7R with IL-7

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 9: Interleukins and interferon gamma

Common γ-chain cytokine familyCytokines

Receptors Signaling Cell sources Cell target

IL-2 (T cell growth factor )

IL-2R 3 units : IL-2α (CD25), IL-2Rβ, common chain

JAK1,JAK3STAT5

CD4+ and CD8+T cellsActivated DCs, NK cells,NKT cells

CD4+ and CD8+

T cells, NKand B cells

IL-4 IL-4R type I (IL-4Rα, common chain)IL-4R type II (IL-4α,IL-13Rα1)

JAK1,JAK3STAT6

TH2 cells, mast cellsbasophils, eosinophilsNKT cells, / T cells.

T and B cellsmacrophage

IL-7(pre-B-cell growth factor, lymphopoietin-1)

IL-7Rα andcommon chain

JAK1,JAK3STAT5

Epithelial cells,keratinocytes,DCs, B cells,and monocytes/macrophages

T cellsProgenitor of B cellBM macrophage

IL-9 IL-9Rα andcommon chain

JAK1,JAK3STAT5

TH2, TH9Mast cells, and eosinophils

B, T, and mastcells

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 10: Interleukins and interferon gamma

Common γ-chain cytokine family

Cytokines

Major functions Disease association

IL-2 Proliferation of effector T and B cellsDevelopment of Treg cellsDifferentiation and proliferation of NK cells Growth factor for B cells

T-cell–mediated autoimmune and inflammatory diseases

X-linked SCID 1 (present nonfunctional B cell)

IL-4 Induction of TH2 differentiation (suppress TH1)IgE class switchupregulation of class II MHC expression on B cells, CD23 and IL-4Rsurvival factor for B and T cellsRegulate allergic conditionsProtective immune response against helminths and other extracellulare parasites

Defective TH2 diferentiation and IgE productionDecrease allergic responseX-linked SCID 1 (present nonfunctional B cell)

IL-7 Survival and proliferation of thymocytesdevelopment of naive and memory B and Tcells , mature T cells, and NK cells

XSCID

IL-9 Important roles in pathogenesis of asthma and allergies and in fighting helminth infectionspromote proliferation of mast cellsinhibition of TH1 cytokinesPromote IgE production, Induce chemokine and mucus production in bronchial epithelial cells

XSCID

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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BIOLOGIC ACTIONS OF IL-2. IL-2 STIMULATES THE PROLIFERATION AND

DIFFERENTIATION OF T AND B LYMPHOCYTES AND NK CELLS. AS DISCUSSED IN THE

TEXT, IL-2 ALSO FUNCTIONS TO INHIBIT IMMUNE RESPONSES (E.G., AGAINST SELF

ANTIGENS) BY ITS EFFECT ON REGULATORY T CELLS.

Page 12: Interleukins and interferon gamma

BIOLOGIC ACTIONS OF IL-4. IL-4 STIMULATES B CELL ISOTYPE SWITCHING TO SOME

IMMUNOGLOBULIN CLASSES, NOTABLY IGE, AND DIFFERENTIATION OF NAIVE T

CELLS TO THE TH

2 SUBSET. IL-4 ALSO INHIBITS TH

1 DIFFERENTIATION.

Page 13: Interleukins and interferon gamma

Common γ-chain cytokine familyCytokines

Receptors Signaling Cell sources Cell target

IL-15(structurally homologous to IL-2)

IL-15RαIL-2Rβcommon chain

JAK1,JAK3STAT5

Monocytes, activated CD4+ T cells,keratinocytes, skeletal muscle cells

T cell (esp. memory)NK cell

IL-21 IL-21Rαcommon chain

JAK1,JAK3STAT3

T cells (predominantly TH17) NKT cells

CD4+ T cells,CD8+ T cells,B cells, DCs,macrophages,keratinocytes

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Common γ-chain cytokine familyCytokines Major functions Disease association

IL-15 T-cell activation,proliferation and activation of NK cellssuppression of IL-2 induced AICD of T cellsHomeostasis of CD81 memory, NK and NKT cells,enhancement of TH2 differentiationand suppression of allergic rhinitis

Absence NK and memory cells

IL-21 B-cell : regulating Ab isotype balance, proliferation,

apoptosis, and differentiation into plasma cellsIncrease cytotoxic activity and proliferation of CD8+ T cells, NK cells, and NKT cells

TH17 cell diferentiation

Decrease TH17 cellsReduce EAE

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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The receptors for IL-3, IL-5, and GM-CSF (GMR) are heterodimers of a unique α-chain and the common β-chain (βc, CD131) subunit

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 16: Interleukins and interferon gamma

Common β chain familyCytokines

Receptors Signaling

Cell sources Cell target

IL-3 IL-3RαCommon β chain (CD131)

JAK2STAT5

T cells,macrophages, NKcells, mastcells, eosinophils,stromal cells

Erythroid progenitors,Granulocyte macrophages progenitors,CD34+ Progenitor cells, basophils, Eosinophils

IL-5(eosinophil and B cell growth factor)

IL-5RαCommon β chain (CD131)

JAK2STAT5

TH2 cellsActivated eosinophils mast cells

Eosinophils,basophils, andmast cells

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Common β chain familyCytokines Major functions Disease associstion

IL-3 Multilineage hematopoietic growth factor during early stage of hematopoiesisActivation of basophils and eosinophils

No detects in basal hematopoiesis

IL-5 promotes proliferation, activation, differentiation, survival, and adhesion of eosinophilsrecruit eosinophils and induction of airway hyperreactivity in asthma

Decrease eosinophil

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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IL-12R consist of 2 subunits, IL-12Rβ1 and IL-12Rβ2.A heterodimer of IL-12Rβ1 and IL-23R bind IL-23. IL-12Rβ2 shows homology to the gp130 subunit of IL-27R

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 19: Interleukins and interferon gamma

IL-12 subfamilyCytokines Receptors Signaling Cell sources Cell target

IL-12(NK stimulating factor)

IL-12Rβ1(p40) andIL-12Rβ2(p35) homologous to gp 130

JAK2TYK2STAT4

Activated monocytes,macrophages,neutrophils,microglia, DCs,B cells

T cells (Th1 cells),NK cells

IL-23 IL-12Rβ1(p40)and IL-23R(p19)

JAK2TYK2STAT3,STAT5

Macrophages,activated DCs

T cells (TH17 cells)and macrophages

IL-27 WSX-1 and gp130

JAK2, TYK2STAT3,STAT4,STAT5

Activated DCs,macrophages,epithelial cells

T cells, NK cells

IL-35 Unknown Unknown Treg cells Different T-cellsubsets

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 20: Interleukins and interferon gamma

IL-12 subfamilyCytokines

Major functions Disease association

IL-12 development and maintenance of TH1 cells by inducing production of IFN-γ by TH1 and NK cellsindirectly activates antimicrobial, antiparasitic, and antitumor activity of macrophages and promotes cytolytic activity of NK cells and lymphokine-activated killer cells

Impaired TH1 response with higher susceptibility to intracellular pathogens

IL-23 Stimulate production of IL-17Promote memory T-cell proliferation

Susceptibility to extracellular pathogens, exacerbate organ-specific autoimmune Inflammation

IL-27 Induction of Tbet promoting TH1-cell differentiationinhibition of TH17-cell response via STAT1

Immune pathology because of uncontrolled inflammatory response

IL-35 Proliferation of Treg cells Inhibition of TH17-cell function,suppression of inflammatory responses

IBD, collagen-inducedarthritis

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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BIOLOGIC ACTIONS OF IL-12.

IL-12 IS PRODUCED BY

MACROPHAGES AND DENDRITIC

CELLS THAT RESPOND TO MICROBES

OR TO T CELL SIGNALS SUCH AS CD40

LIGAND ENGAGING CD40. IL-12 ACTS

ON T LYMPHOCYTES AND NK CELLS

TO STIMULATE IFN- Γ PRODUCTION

AND CYTOTOXIC ACTIVITY, BOTH OF

WHICH FUNCTION TO ERADICATE

INTRACELLULAR MICROBES.

Page 22: Interleukins and interferon gamma

The receptors for IL-4 and IL-13 consists of 2 receptor chains, the IL-4Rα (CD124) and the common γc. IL-4 and IL-13 bind to IL-4R, which consists of the IL-4Rα and the IL-13Rα1 chain. IL-13R consists of 2 subunits, IL-13Rα1 and IL-13Rα2 , and signaling occurs via the IL-4R complex type II that consists of the IL-4Rα and IL-13Rα

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Th2-like cytokinesCytokines Receptors Signalings Cell sources Cell target

IL-13 IL-13Rα1 (activate)IL- 13Rα2(inhibit,fibrosis)

JAK1TYK2STAT6

TH2 cell NKTmast cells basophils,eosinophils

B cellsMast cells, epithelial cells, Eosinophilssmooth muscle cellsmacrophages

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Th2-like cytokinesCytokines Major functions Disease association

IL-13 Switching to IgG4 and IgEupregulation of CD23, MHC-II on B cellsinduction of CD11b, CD11c, CD18, CD29; CD23, and MHC-II on monocytes,activation of eosinophils and mast cellsrecruitment and survival of eosinophils Defense against parasite Infections

Asthma, allergic rhinitis, fibrosisairway remodeling

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Gp 130 utilizingCytokines

Receptors

signalings Cell sources Cell target

IL-6 IL-6Rαgp130

JAK1STAT3

Endothelial cells,fibroblasts,monocytes/ macrophages

Hepatocytes,leukocytes,T cells, B cells,hemopoietic cells

IL-11 IL-11Rαgp130

JAK1STAT3

Stromal cells:fibroblasts,epithelial cells,endothelialcells, vascularsmooth musclecells, synoviocytes,osteoblasts

Myeloid,erythroid, andmegakaryocyteprogenitors,osteoclasts,epithelial cells,hepatocytes,macrophages,neurons

IL-31 IL-31 RA/OSMRb (oncostatin-M rreceptor β)

JAK1STAT3STAT5

Activated CD4+T cells (mainly TH2)and CD8+ T cells

Keratinocytes,epithelial cells,monocytes,eosinophils,basophils

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Gp 130 utilizingCytokines Major functions Disease association

IL-6 Liver: synthesis of acute phase proteins;leukocytes: trafficking, activation;T cell: differentiation, activation, survival;B cell: differentiation, production of IgG, IgM, IgAHematopoiesis

Autoimmune disease,Chronic inflammatory disease, B-cellmalignancy, SLE, Castleman disease,plasmacytoma/ multiple myeloma

IL-11 Growth factor for myeloid, erythroid, and megakaryocyte progenitors;Bone remodeling;Protects epithelial cells and connective tissue; induction of acute-phase protein; Inhibition of macrophage activity;promotion of neuronal development

rIL-11 approved for treatment of thrombocytopenia (post chemotherapy)

IL-31 Induces chemokinesPMN recruitment

Atopic dermatitis,allergic contact dermatitis, prurigo nodularis, chronic spontaneous urticaria, nonatopiceczema, asthma, other inflammatory disorders

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 27: Interleukins and interferon gamma

IL-10 family members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29.They share common receptor subunits shown

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 28: Interleukins and interferon gamma

IL-10 family

Cytokines Receptors Signalings Cell sources Cell target

IL-10 IL-10R1/IL-10R2complex

JAK1TYK2STAT3

T cells (Tr1) , B cells,monocytes,macrophages,DCs

Macrophages,monocytes,T cells, B cells,NK cells, mast cells,DC andgranulocytes

IL-19 IL20R1/IL-20R2

STAT1STAT3

Monocytes,T cellkeratinocytes,airway epithelialcells and B cells

KeratinocytesT cell

IL-20 IL-20R1/IL-20R2and IL-22R1/IL-20R2

STAT1STAT3

Monocytes,keratinocytes,epithelial andendothelial cells

Keratinocytes,monocytes

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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IL-10 familyCytokines Major functions Disease association

IL-10 Immune suppressiondownregulating the expression of MHC class II and costimulatory molecules on macrophages and monocytesinhibits the expression of many proinflammatory cytokines, chemokines, and chemokine receptorspromotes survival, proliferation,and differentiation of human B cells and increases the production of IgG4

Cancer,autoimmunity,allergy

IL-19 proinflammatory responses (stimulatesproduction of IL-6 and TNF-α)might promote TH2-cell

AsthmaPsoriasis

IL-20 Role in skin biologyrole in pathogenesis of psoriasis

Psoriasis, RA,atherosclerosis

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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IL-10 familyCytokines Receptors Signalings Cell sources Cell target

IL-22 IL-10R2 chainand IL-22R1 chain

STAT1STAT3

Activated T cells(predominantlyTH17,TH22), NKT cells (NK-22)

Tissue cells likekeratinocytes,subepithelialmyofibroblasts

IL-24 (melanoma differentiation associated gene -7)

IL20R1/IL-20R2and IL-22R1/IL-20R2

STAT1STAT3

Melanocytes, T cells,monocytes

Cancer cells

IL-26 IL-10R2 chain andIL-20R1 chain

STAT1STAT3

Activated T cells(predominantlyTH17), NKT cells

Epithelial cells

IL-28A/B,IL-29(IFN λ family)

IL-28R1/IL-10R2

STAT1-5 Monocyte-derivedDCs

Most cell types

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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IL-10 family

Cytokines Major functions Disease association

IL-22 Pathogen defense,Induce production of inflammatory cytokines,TH2 response

Psoriasis, IBD,cancer

IL-24 Tumor suppression Melanoma,psoriasis

IL-26 Activation and regulation of epithelial cells

IBD

IL-28A/B,IL-29(IFN λ family)

Antiviral immunityinhibit replication of hepatitis B and C viruses

Role in allergic andAutoimmune diseases

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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IL-1 familyCytokines Recepto

rs Signalings

Cell sources Cell target

IL-1α, IL-1β(human leukocyte pyrogen)Caspase-1(IL-1β)

IL-1RIIL-1RII (decoy receptor)

IRAKMyD88TRAF6NF-κB,AP-1

Activated macrophages,M,L,keratinocytes,microglia, megakaryocytes,N,fibroblasts, synovial lining cells

T cells, fibroblasts,epithelial andendothelial cells

IL-1Ra(antagonist)

IL-1RI, IL-1RII Same as IL-1 T cells, fibroblasts,epithelial andendothelial cells

IL-18Caspase-1

IL-18R IRAKMyD88TRAF6NF-κB

macrophages,Kupffer cells,keratinocytes,osteoblasts,astrocytes, DCs

T cells, NK cells,macrophages,epithelial cells,chondrocytes

IL-33 ST2 Necrotic cells andnuocytes

Basophils, mast cells,eosinophils, NKcells, NKT cells,TH2 cells, DCs,

IL-37 (IL-1F) IL-18Rα? Monocytes, tonsilplasma cells, breastcarcinoma cells

Intracellularmechanism mannerand DC

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 34: Interleukins and interferon gamma

IL-1 familyCytokines Major functions Disease association

IL-1α, IL-1β Induction of proinflammatory cytokines(endogenous pyrogen ),Diverse potentiating effects on cell proliferation,differentiation and function of many innate and specific immunocompetent cells

Wide range of autoimmune and inflammatory diseases, RA, IBD,Psoriasis

IL-1Ra(antagonist)

Antagonism of IL-1 Wide range of autoimmune andInflammatory diseases, RA, IBD,Psoriasis

IL-18 Induction of IFN-γ in presence of IL-12, enhances NK cell cytotoxicity, promoting TH1 or TH2–cell responses depending cytokine milieu

Autoimmune diseasesor inflammatory disorders, RA,psoriasis, MS, type I diabetes

IL-33 Transcriptional repressor activity,Potent induction of TH2 inflammation

Autoimmune and cardiovasculardiseases, asthma, GI tractand lung disorders

IL-37 Suppression of proinflammatory cytokines andinhibition of DC activation

RA

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 35: Interleukins and interferon gamma

IL-17 familyCytokines Receptors Cell sources Cell target

IL-17A IL-17RA(=IL-17R)

TH17 cells(expose to IL-1β,IL-6,IL-23,TGF=β),CD8+

T cells, NK cells,NKT cells, γδ T cells, neutrophils

Epithelial/endothelial cells, fibroblasts, osteoblasts,Monocytes,macrophages

IL-17B,C,D For IL-17 B, IL-17RB (=IL-17H1,IL25R); for IL-17C and D,not known

IL-17B: neuronal cells, chondrocytes;IL-17C: immune cells under certain conditions; IL-17D: resting B and T Cells

Monocytes,endothelial cells,myofibroblasts

IL-17F IL-17RA (=IL-17R)and IL-17RC(IL-17RL)

TH17 cells, CD8+T cells, NK cells, NKT cells, γδ T cells, neutrophils

Epithelial/endothelialcells, fibroblasts,osteoblasts,monocytes,macrophages

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 36: Interleukins and interferon gamma

IL-17 family

Cytokines Major functions Disease association

IL-17A Induction of proinflammatory cytokines,chemokines, and metalloproteases;recruitment of Neutrophils

RA, MS, IBD,psoriasis, allergic asthma, atopic dermatitis, contactHypersensitivity

IL-17B,C,D Induction of proinflammatory cytokines,chemokines, and metalloproteases;IL-17B: chondrogenesis and osteogenesis

RA, allergic asthma,inflammatorycardiomyopathy,Wegener granuloma

IL-17F Induction of proinflammatory cytokines,chemokines, and metalloproteases;recruitment of Neutrophils

IBD, psoriasis, allergicasthma

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Th2-like cytokinesCytokines Receptors Cell

sources Cell target

Major functions

Disease association

IL-25 (IL-17E)

IL-17RAandIL-17RBTRAF2

TH2 cells, mast andepithelial cells,eosinophils andbasophils fromatopic individuals

TH2 memorycells

Induction of TH2responses, IgE,IgG1, IL-4, IL-5, IL-13, and IL-9production

Gl disorders,Asthma

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

Page 38: Interleukins and interferon gamma

IL with chemokine activity

Cytokines Receptors Cell sources

Cell target

Major functions

Disease association

IL-8 (neutrophil specific chemotactic factor)

CXCR1(IL-8RA) andCXCR2(IL-8 RB)

Monocytes,macrophages,neutrophils,lymphocytes,endothelial cells,epithelial cells,fibroblasts,keratinocytes,chondrocytes,synovial cells,hepatocytes

Neutrophils, NKcells, T cells,basophils,eosinophils,endothelialcells

Activation and recruitment ofneutrophils, NK cells, T cells,basophils,eosinophils;mobilization ofhematopoieticstem cells;angiogenesis

Increased levelsduringinflammatorydiseases (RA,psoriasis,bacterial andviral infections)

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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Type II interferonCytokines

Receptors

Cell sources

Cell target Major functions

Disease associstion

IFN-γ IFNGR1/IFNGR2

NK and NKT cells,macrophages,myelomonocyticcells, Th1 cells,CTL and B cells

Epithelial cells,macrophages, DCs,NK cells, T and Bcells

Antiviral properties,promotes cytotoxicactivity, TH1 differentiation,upregulation ofMHC class I and II,inhibition of cellgrowth,proapoptotic effectsand control ofAICD,isotype swithing to IgG2a, andenhancement ofmicrobial killingability

Susceptibility tointracellularpathogen infectionand tumordevelopment, type1 diabetes, RA,experimentalautoimmuneencephalomyelitis

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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CLINICAL APPLICATION anakinra (rIL-1 receptor antagonist),

approved for use in RA1 (less effective than TNFα blocking agent)

SoJIA,adult-onset Still disease Rilonacept (IL-1 Trap) and canakinumab

(anti-IL-1β monoclonal)1

approved for use in cryopyrin-associated periodic syndromes (CAPS) (level A)

2.Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

1.Ann Rheum Dis 2011;70(Suppl 1):i2–i36.

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CLINICAL APPLICATION Antagonist IL-2Rα mAbs

(anti-Tac/Daclizumab, basiliximab) Prevent rejection of organ transplants T cell mediated autoimmune disease ass.

Abn. of IL-2/IL-2R system, noninfectious uveitis

IL-2(proleukin) Immune adjuvant in lymphoproliferative

disease and cancer (dose limiting toxicity)metastatic melanoma and metastatic renal

cell carcinoma (FDA approved)

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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CLINICAL APPLICATION Tocilizumab ( humanised anti-IL-6 receptor

mAb) use in moderate to severe RA,incomplete

responders to TNF-antagonist (FDA,cat D)

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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CLINICAL APPLICATION Anti IL-5Ab (mepolizumab,reslizumab)

Asthma (refractory eosinophilic ,steroid dependent with sputum eosinophilia)

Subgroup of hypereosiniphilic syndrome (lymphocytic varient)

Anti IL-13Ab in high grade astroma rIL-11 approved for treatment of

thrombocytopenia induced by chemotherapy

Anti IL-23Ab in Crohn disease

Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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CLINICAL APPLICATION

ustekinumab (Stelara) for plaque psoriasis (FDA approved )

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CONCLUSION Interleukin :cytokines made by

leukocyte and act on other leukocyte Secretion is brief,self limited Often influence the synthesis and action

of other cytokines Effect

Pleiotropic redundancy

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FUNCTIONS OF SELECTED CYTOKINES IN HOST DEFENSE

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ROLES OF CYTOKINES IN HEMATOPOIESIS.DIFFERENT CYTOKINES STIMULATE THE GROWTH AND MATURATION OF DIFFERENT LINEAGES OF BLOOD CELLS