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. 2010 Oct;2(5):247-56.
doi: 10.1177/1759720X10378372.

The role of interleukin 6 in the pathophysiology of rheumatoid arthritis

Srinivasan Srirangan  1 , Ernest H Choy
Affiliations

The role of interleukin 6 in the pathophysiology of rheumatoid arthritis

Srinivasan Srirangan et al. Ther Adv Musculoskelet Dis. 2010 Oct.

Abstract

Interleukin 6 (IL-6) is a pleiotropic cytokine with a pivotal role in the pathophysiology of rheumatoid arthritis (RA). It is found in abundance in the synovial fluid and serum of patients with RA and the level correlates with the disease activity and joint destruction. IL-6 can promote synovitis and joint destruction by stimulating neutrophil migration, osteoclast maturation and vascular endothelial growth factor (VEGF)-stimulated pannus proliferation. IL-6 may also be mediating many of the systematic manifestations of RA including inducing the acute-phase reaction [including C-reactive protein (CRP)], anaemia through hecipidin production, fatigue via the hypothalamic-pituitary-adrenal (HPA) axis) and osteoporosis from its effect on osteoclasts. In addition, IL-6 may contribute to the induction and maintenance of the autoimmune process through B-cell maturation and TH-17 differentiation. All of the above makes IL-6 blockade a desirable therapeutic option in the treatment of RA. Following successful animal studies, a humanized anti-interleukin-6 receptor (anti-IL-6R) monoclonal antibody, tocilizumab (TCZ), entered into clinical trials and it has been shown to be an effective treatment in several large phase III clinical trials in RA with rapid and sustained improvement in disease activity, reducing radiographic joint damage and improving physical function.

Keywords: interleukin 6; pathophysiology; receptor blockade; rheumatoid arthritis.

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Conflict of interest statement

E.C. has received research grants and honoraria from Roche and from Allergan, Boehringer Ingelheim, Chelsea Therapeutics, Eli Lilly, GSK, Jazz Pharmaceuticals, Merrimack Pharmaceutical, MSD, Pfizer, Pierre Fabre Medicament, Schering-Plough, UCB Celltech and Wyeth for advisory boards, consultancy and speaker bureaus. The other author has declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Inflammatory pathways activated by interleukin (IL)-6. In the joints IL-6 induces pannus formation, osteoclast activation and mediates chronic synovitis.
Figure 2.
Figure 2.
Systemic effects of IL-6.
See this image and copyright information in PMC

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