Main Article Content


Rheumatoid arthritis (RA) is a systemic autoimmune disorder with an unknown etiology. It typically affects the peripheral synovial joints symmetrically. The roles of T and B cells, macrophages, plasmocytes, host tissue cells (synoviocytes, chondrocytes), and osteoclasts
in RA are more defi ned. In RA, cytokines secreted by cells implicated in adaptive and natural immunity have important roles in causing infl ammation, articular destruction, and other comorbid diseases related to RA. Other than the clear roles of interleukin (IL)-1 and tumor necrosis factor α, there are other cytokines that are suspected of having roles in the pathogenesis of RA, IL-17 for instance. Interleukin-17 is a proinfl ammatory cytokine,  produced by Th17 cells, and has pleiotropic effects on various cells contributing to the pathogenic condition of RA. Several studies showed that this cytokine maintains the infl ammation and causes more destruction of joint cartilage. Advances in the understanding of the role of IL-17 elicits the idea to modulate IL-17 and/or Th17 cells as the potential targets
of therapy in RA

Article Details

How to Cite
Ongkowijaya, J. A., Setiyohadi, B., Sumariyono, S., & Kasjmir, Y. I. (2018). Role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Indonesian Journal of Rheumatology, 2(1).


  1. Scott DL, Kingsley GH. Rheumatoid arthritis. In: Scott DL, Kingsley GH, editors. Infl ammatory arthritis in clinical practice. London: Springer Verlag; 2008. p. 1–31.
  2. Emmi L, Romagnami S. Role of Th1 and Th2 cells in autoimmunity. In: Rose NR, Mackay IR, editors. The autoimmune diseases. 4th ed. St.Louis: Elsevier; 2006. p. 83–102.
  3. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells.N Eng J Med 2009;361:888–98.
  4. Fox DA. Etiology and pathogenesis of rheumatoid arthritis. In: Koopman WJ, Moreland LW, editors. Arthritis and allied conditions: a textbook of rheumatology. 15th ed. Philadelphia: Lippincott Williams and Wilkins;2005. p. 1089–115.
  5. Agarwal V, Malaviya AN. Cytokine network and its manipulation in rheumatoid arthritis. J Indian Rheumatol Assoc 2005;13:86–91.
  6. Brennan FM, McInnes B. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 2008;118:3537–45.
  7. Kirkham BW, Lassere MN, Edmonds JP, Juhasz KM, Bird PA, Lee CS, et al. Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). Arthritis Rheum 2006;54:1122–31.
  8. Yago T, Nanke Y, Kawamoto M, Furuya T, Kobashigawa T, kamatani N, et al. IL-23 induces human osteoclastogenesis via IL-17 in vitro and anti–IL- 23 antibody attenuates collagen-induced arthritis in rats. Arthritis ResTher 2007;9(5):R96.
  9. Abbas AK, Lichtman AH, Pillai S. Cytokines. In: Abbas AK, Lichtman AH, Pillai S, editors. Cellular and molecular immunology. 6th ed. Philadelphia:Saunders; 2007. p. 267–301.
  10. McInnes IB. Cytokines. In: Firestein GS, Budd RC, Harris Jr ED, McInnes IB, Ruddy S, Sergent JS, editors. Kelley’s textbook of rheumatology. 8th ed. Philadelphia: Saunders; 2009. p. 367–78.
  11. Haugeberg G, Orstavik RE, Kvien TK. Effect of rheumatoid arthritis on bone. Curr Opin Rheumatol 2003;15(4):469–75.
  12. Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fl uid cytokine profi le of T cell and stromal cell origin. Arthritis Res Ther2005;7:R784–95.
  13. Miossec P. Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to infl ammation and destruction through synergy. ArthritisRheum 2003;48(3):594–601.
  14. Miossec P. Interleukin-17 in fashion, at last: ten years after its description, its cellular source has been identifi ed. Arthritis Rheum 2007;56:2111–5.
  15. Romagnani S. Human Th17 cells. Arthritis Res Ther 2008;10:206–13.
  16. Chen Z, O’Shea J. Regulation of IL-17 production in human lymphocytes. Cytokine 2008;41(2):71–8.
  17. Lubbets E, Koenders MI, van den Berg WB. The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models.Arthritis Res Ther 2005;7:29–37.
  18. Anderson AK, Li C, Brennan FM. Recent developments in the immunobiology of rheumatoid arthritis. Arthritis Res Ther 2008;10:204–12.
  19. Gabay C. Cytokines and cytokine receptors. In: Koopman WJ, Moreland LW, editors. Arthritis and allied conditions: a textbook of rheumatology.
  20. th ed. Philadelphia: Lippincott Williams and Wilkins; 2005. p. 423–76.
  21. Cope AP. T-cells in rheumatoid arthritis. Arthritis Res Ther 2008;10(Supl1): S1–10.
  22. Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, et al. Human interleukin-17: a T cell-derived proinfl ammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 1999;42:963–70.
  23. Kohno M, Tsutsumi A, Matsui H, Sugihara M, Suzuki T, Mamura M, et al. Interleukin-17 gene expression in patients with rheumatoid arthritis. Mod
  24. Rheumatol 2008;18:15–22.
  25. Shahrara S, Huang QQ, Mandelin II AM, Pope RM. Th17 cells in rheumatoid
  26. arthritis. Arthritis Res Ther 2008;10:R93–9.
  27. Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P. IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res 2001;3:168–77.
  28. Jovanovic DV, DiBattista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, et al. IL-17 stimulates the production and expression of proinfl ammatory cytokines, IL-beta and TNF alpha, by human macrophages. J Immunol1998;160:3513–21.
  29. Katz Y, Nadiv O, Beer Y. Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins 1, 6, and 8 in skin and synovialfi broblasts: a possible role as a “fi ne-tuning cytokine†in infl ammationprocesses. Arthritis Rheum 2001;44:2176–84.
  30. Chabaud M, Fossiez F, Taupin JL, Miossec P. Enhancing effect of IL-17 on IL-1–induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol1998;161:409–14.
  31. Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P. Contribution of interleukin-17 to synovium matrix destruction in rheumatoid arthritis. Cytokine 2000;12(7):1092–9.
  32. Cai L, Yin JP, Starovasnik MA, Hogue DA, Hillan KJ, Mort JS, et al. Pathways by which interleukin-17 induces articular cartilage breakdown in vitro and in vivo. Cytokine 2001;16:10–21.
  33. van Bezooijen RL, van der Wee-Pals L, Papapoulos SE, Lowik CWGM. Interleukin-17 synergizes with tumor necrosis factor ï¡ to induce cartilage destruction in vitro. Ann Rheum Dis 2002;61:870–6.
  34. Koshy PJ, Henderson N, Logan C, Life PF, Cawston TE, Rowan AD. Interleukin-17 induces cartilage breakdown: novel synergistic effects in combination with proinfl ammatory cytokines. Ann Rheum Dis2002;61:704–13.
  35. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fl uids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999;103(9):1345–52.
  36. Yamada H, Nakashima Y, Okazaki K, Mawatari T, Fukushi JI, Kaibara N et al. Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:1299–304
  37. Bessis N, Boissier MC. Novel proinfl ammatory interleukins: potential therapeutic targets in rheumatoid arthritis. Joint Bone Spine 2001;68(6):477–81.
  38. Lubberts E. IL-17/Th17 targeting on the road to prevent chronic destructive arthritis. Cytokine 2008;41(2):84–91.
  39. Koenders M, Joosten LAB, van den Berg WB. Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumor necrosis factor and IL-1 in experimental arthritis. Ann Rheum Dis 2006;65(supplIII):iii29–33.
  40. Genovese MC, van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, et al. LY2439821, a humanized anti–interleukin-17 monoclonalantibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis and Rheumatism. 2010;62(4):929–39