Interleukin-27 in rheumatic diseases: Friend or foe? Comment on the article by Pickens et al
Article first published online: 31 AUG 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 9, page 2832, September 2011
How to Cite
Yuan, F.-L., Li, X., Sun, J.-M. and Xu, R.-S. (2011), Interleukin-27 in rheumatic diseases: Friend or foe? Comment on the article by Pickens et al. Arthritis & Rheumatism, 63: 2832. doi: 10.1002/art.30495
- Issue published online: 31 AUG 2011
- Article first published online: 31 AUG 2011
- Accepted manuscript online: 23 JUN 2011 03:00PM EST
- China National Science Foundation. Grant Number: 30901526
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).
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- 3Interleukin-27 and interferon-γ are involved in regulation of autoimmune arthritis. J Biol Chem 2011; 286: 2817–25., , , .
- 4IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J Immunol 2008; 180: 922–30., , , .
- 5Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27. J Immunol 2004; 173: 1171–8., , , , .
- 6Effects of inflammatory cytokine IL-27 on the activation of fibroblast- like synoviocytes in rheumatoid arthritis. Arthritis Res Ther 2010; 12: R129., , , , , .
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Feng-Lai Yuan MD, PhD*, Xia Li MD*, Jun-Ming Sun MD*, Rui-Sheng Xu MD, PhD*, * Third Hospital, Nantong University, Jiangsu, China.