interleukins and interferon gamma
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Interleukins And Interferon-gamma: Receptors,Functions, And Roles In Diseases
Boonthorn
8 April 2011
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)
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
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
CLASSIFICATION TH2-like cytokines : IL-5,IL-13,IL-25,IL-31 ILs with chemokine activity : IL-8,IL-16
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
CLINICAL APPLICATION
ustekinumab (Stelara) for plaque psoriasis (FDA approved )
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
FUNCTIONS OF SELECTED CYTOKINES IN HOST DEFENSE
ROLES OF CYTOKINES IN HEMATOPOIESIS.DIFFERENT CYTOKINES STIMULATE THE GROWTH AND MATURATION OF DIFFERENT LINEAGES OF BLOOD CELLS