Interleukins and interferon-gamma are secreted proteins that bind to specific receptors and communicate between leukocytes. They are classified based on sequence homology and receptor similarities or functions. Interleukins signal through pathways like JAK-STAT and have pleiotropic and redundant effects. Their receptors are organized into families like the common gamma chain family and are involved in processes like hematopoiesis, immune cell differentiation, and host defense. Blocking interleukins clinically helps treat diseases associated with their abnormal functions such as rheumatoid arthritis, cancer, and asthma.

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

2. 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)

3. classification Type I cytokines (contain WSXWS) gp 130-utilizing : IL-6,IL-11,IL-27,IL-31 β chain utilizing : IL-3,IL-5  chain utilizing : IL-2,IL-4,IL-7,IL-9,IL-15,IL-21 Hetero-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

5. 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

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

7. 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.

8. 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.

9. Common γ-chain cytokine family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

10. Common γ-chain cytokine family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

11. 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.

12. 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 TH2 subset. IL-4 also inhibits TH1 differentiation.

13. Common γ-chain cytokine family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

14. Common γ-chain cytokine family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

15. 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.

16. Common β chain family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

17. Common β chain family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

18. 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.

19. IL-12 subfamily Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

20. IL-12 subfamily Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

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.

22. 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.

23. Th2-like cytokines Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

24. Th2-like cytokines Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

25. Gp 130 utilizing Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

26. Gp 130 utilizing Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

27. 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.

28. IL-10 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

29. IL-10 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

30. IL-10 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

31. IL-10 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

33. IL-1 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

34. IL-1 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

35. IL-17 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

36. IL-17 family Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

37. Th2-like cytokines Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

38. IL with chemokine activity Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

39. Type II interferon Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

40. 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) 1.Ann Rheum Dis 2011;70(Suppl 1):i2–i36. 2.Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

41. Clinical application Antagonist IL-2RαmAbs (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.

42. Clinical application Tocilizumab ( humanised anti-IL-6 receptor mAb) use in moderate to severe RA,incompleteresponders to TNF-antagonist (FDA,cat D) Akdis et al.J Allergy Clin Immunol 2011;127:701-21.

43. 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.

44. Clinical application ustekinumab(Stelara) for plaque psoriasis (FDA approved )

45. 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

46. Functions of selected cytokines in host defense

47. Roles of cytokines in hematopoiesis.Different cytokines stimulate the growth and maturation of different lineages of blood cells