A recently released study underscores the important proinflammatory role of interleukin-18 (IL-18) in the pathophysiology of inflammatory arthritis, and suggests that treatment that inhibits or neutralizes endogenous IL-18 may become an effective tool in controlling synovial tissue inflammation.

While early studies have highlighted the role of IL-18 expression in established RA, this is the first to demonstrate elevated serum and synovial tissue IL-18 expression in other categories of inflammatory arthritis, including undifferentiated seronegative arthritis, psoriatic arthritis, and reactive arthritis, reported lead investigator Terence Rooney, MD, and colleagues at St. Vincent's University Hospital in Dublin, Ireland.

The researchers observed that following 1 year of treatment with either methotrexate or sulphasalazine, synovial tissue biopsies revealed decreases in IL-18 tissue expression in 8 of the 12 patients (5 RA, 4 seronegative arthritis, and 3 psoriatic arthritis patients), a finding deemed statistically significant (P = .068). Notably, "tissue IL-18 expression, but not serum levels, correlated significantly with the acute-phase response," Dr. Rooney and colleagues wrote in Annals of Rheumatic Disease.

"Several investigators around the world have identified IL-18 as an important cytokine, both in RA and psoriatic arthritis," Paul P. Tak, MD, PhD, director of the Division of Clinical Immunology and Rheumatology at the University of Amsterdam, The Netherlands, said in an interview with CIAOMed. "However, the importance of this study is that it shows cytokines at the site of inflammation in the synovial tissue."

Christy C. Park, MD, assistant professor of medicine at the Northwestern University Feinberg School of Medicine, in Chicago, Illinois, added that "this study complements the notion that cytokine blockade is an effective treatment strategy, because patients treated with DMARDs had a corresponding decrease in cytokine expression."

Dr. Rooney and his team obtained synovial tissue biopsies and serum samples from 28 patients (12 with RA, 9 with undifferentiated seronegative arthritis, 5 with psoriatic arthritis, and 2 with reactive arthritis) before treatment with methotrexate or sulphasalazine; 12 patients also consented to have tissue biopsy after 1 year of treatment.

Immunohistochemical staining was used to determine IL-18 expression in tissue, while an enzyme-linked immunoassay was used to measure IL-18 expression in serum. At baseline, the researchers found that tissue IL-18 expression was increased in all diagnostic groups, compared with tissue taken from patients with osteoarthritis (P < .05).

A significant correlation was also observed between changes in tissue IL-18 and C-reactive protein (CRP) levels (R = .72, P = .009). This correlation, the researchers noted, has a potential clinical implication since CRP levels are routinely monitored in RA patients. "It suggests that when CRP declines, inflammatory cytokine levels may also be decreasing," Dr. Park said.

The study may also be of clinical importance because although a large body of work exists on the positive effects of tumor necrosis factor-α blockade in inflammatory arthritis, many patients are suboptimal responders to that form of therapy. Therefore, there is "clear need for other treatment options and IL-18 would be a good candidate target," Dr. Park said.

Reference

Rooney T, Murphy E, Benito M, et al. Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis. Ann Rheum Dis. 2004;63:1393-1398.