Blood Levels of the New Anti-Inflammatory Cytokine IL-37 Are Increased In Rheumatoid Arthritis Patients

Blood Levels of the New Anti-Inflammatory Cytokine IL-37 Are Increased In Rheumatoid Arthritis Patients

A recent study published in PLoS One suggests that interleukin (IL)-17 is involved in a control circuit that tries to regulate inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with increased levels of pro-inflammatory cytokines such as IL-6, IL-17A and tumor necrosis factor (TNF)-α.

Early intervention and treatment of RA is based on disease-modifying anti-rheumatic drugs (DMARDs), which are aimed to reduce synovial inflammation and damage, as well as, local or systemic cytokine production.

IL-37 is a new member of the anti-inflammatory cytokine family, described in 2000, and like IL-1 and IL-18, is produced as a precursor that must be cleaved by caspase-1 to be activated.

IL-37 is considered a natural suppressor of pro-inflammatory cytokines production and excessive inflammation, acting presumably as a negative feedback inhibitor of inflammatory responses, a function that is not dependent on anti-inflammatory cytokines such as IL-10 (Marcel F Nold et al., 2010; Jacques Banchereau et al., 2012).

Previous research indicates that IL-37 is increased in plasma of patients with severe systemic lupus erythematosus (SLE), lamina propria macrophages of patients with Crohn’s disease, and the synovial tissue of RA patients. However, systemic IL-37 levels and the correlation between IL-37 and disease activity in RA patients have not yet been investigated.

In the study published in PLoS One, Ping-Wei Zhao and colleagues, from the Jilin University, Changchun, China, evaluated pro- and anti-inflammatory cytokine profiles in 50 newly diagnosed RA patients, before and after DMARD therapy with methotrexate and leflunomide.

In this study, the authors found that plasma levels of IL-37 were elevated in RA patients, and the IL-37 concentrations positively correlated with the levels of TNF-α and IL-17A, and also with the disease activity, as evidenced by CRP levels. Patients that qualified as good DMARDs-treatment responders had down-regulated IL-17A, IL-6 and TNF-α expression but also IL-37 levels.

This relatively small study indicates that IL-37 production is most likely induced by pro-inflammatory cytokines during an active disease such as RA.

The authors suggest that this new anti-inflammatory cytokine may be part of a feed-back loop that is aimed to restrict inflammation, a mechanism that may be dysfunctional in rheumatoid arthritis.

Source: PLoS One, 2014, 9(5):e95346. doi: 10.1371/journal.pone.0095346. eCollection 2014
Read more: PLoS One

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