To the Editor:

In a recent study reported in Arthritis & Rheumatism, Pickens et al confirmed in vivo that injection of adenoviral interleukin-27 (IL-27) transcript into the ankles of mice with collagen-induced arthritis (CIA) attenuates joint inflammation, synovial lining thickness, bone erosion, and leukocyte migration (1). Additionally, IL-27 treatment resulted in reduced IL-1β and IL-6 production in mice with CIA. Moreover, IL-27 suppressed Th17 cell differentiation as well as downstream IL-17 target genes, leading to decreased IL-17–mediated monocyte recruitment and angiogenesis, possibly through reduction of neutrophil and monocyte chemokines. They concluded that IL-27 may therefore be a promising target for therapeutic intervention to control disease in patients with rheumatoid arthritis (RA) (1).

This interesting study provides valuable data on the role of IL-27 in RA. In fact, another study also demonstrated that administration of IL-27 could attenuate CIA development at the onset of disease, by suppression of IL-17 and IL-6 synthesis (2). Further, Rajaiah et al (3) showed that treatment with exogenous IL-27 successfully controlled arthritis-related inflammation and inhibited mediators of inflammation, angiogenesis, cell survival, apoptosis, and tissue damage in adjuvant-induced arthritis (AIA), by reducing matrix metalloproteinase 9 (MMP-9) activity, vascular endothelial growth factor secretion, and phosphorylated Akt.

However, the available data seem to be controversial. In several previous studies, IL-27 was detected in the synovial membrane and synovial fluid of patients with RA and was reported to induce a Th1 immune response and susceptibility to proteoglycan-induced arthritis (4). Consistent with these findings, anti–IL-27 antibody treatment or IL-27 receptor knockout has been found to suppress ongoing severe inflammation and proinflammatory cytokine production in AIA (5). Moreover, recently published data suggested that IL-27 could stimulate other nonimmune cell targets, such as fibroblast-like synoviocytes (FLS), in the joints and induce the expression of adhesion molecules on the cell surface of FLS and the release of chemokines and MMP-1 in RA FLS (6, 7).

Overall, based on immunologic evaluations it appears that IL-27 exerts profound antiinflammatory effects in RA models (“friend”) but at the same time plays a proinflammatory role in rheumatic diseases (“foe”). In order to ascertain the exact mechanisms of action of IL-27 in rheumatic diseases and determine whether it is truly a friend or foe, further studies with large sample sizes and precise methodology are needed, especially in human systems.


Supported by the China National Science Foundation (grant 30901526).

  • 1
    Pickens SR, Chamberlain ND, Volin MV, Mandelin AM II, Agrawal H, Matsui M, et al. Local expression of interleukin-27 ameliorates collagen-induced arthritis. Arthritis Rheum 2011; 63: 228998.
  • 2
    Niedbala W, Cai B, Wei X, Patakas A, Leung BP, McInnes IB, et al. Interleukin 27 attenuates collagen-induced arthritis. Ann Rheum Dis 2008; 67: 14749.
  • 3
    Rajaiah R, Puttabyatappa M, Polumuri SK, Moudgil KD. Interleukin-27 and interferon-γ are involved in regulation of autoimmune arthritis. J Biol Chem 2011; 286: 281725.
  • 4
    Cao Y, Doodes PD, Glant TT, Finnegan A. IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J Immunol 2008; 180: 92230.
  • 5
    Goldberg R, Wildbaum G, Zohar Y, Maor G, Karin N. Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27. J Immunol 2004; 173: 11718.
  • 6
    Wong CK, Chen DP, Tam LS, Li EK, Yin YB, Lam CW. Effects of inflammatory cytokine IL-27 on the activation of fibroblast- like synoviocytes in rheumatoid arthritis. Arthritis Res Ther 2010; 12: R129.
  • 7
    Fearon U. Interleukin-27: a master regulator in inflammation [editorial]. Arthritis Rheum 2011; 63: 215760.

Feng-Lai Yuan MD, PhD*, Xia Li MD*, Jun-Ming Sun MD*, Rui-Sheng Xu MD, PhD*, * Third Hospital, Nantong University, Jiangsu, China.