Background/Purpose: Characterized as a fundamental inhibitor of innate inflammation, IL‑1 family member IL‑37 is expressed in the synovia of patients with rheumatoid arthritis. We investigated the role of IL‑37 in joint inflammation and the effects of IL‑37 treatment on joint pathology in a mouse model of experimental arthritis.

Methods: Wild‑type mice were subjected to acute arthritis and peritonitis by instillation of streptococcal cell wall (SCW) fragments, and treated with a recombinant form of the naturally occurring human IL‑37. SCW‑induced arthritis was induced also in mice transgenic for human IL‑37 (IL‑37tg). The severity of joint and systemic inflammation, changes in IL‑37 gene expression, joint histology, and local and systemic cytokine and chemokine production were determined. 

Results: In wild‑type mice, low doses of recombinant IL‑37 suppressed joint inflammation by 51.7% (p<0.001), and significantly decreased synovial IL‑1β by 84%, IL‑6 by 73%, TNFα by 33%, KC by 58%, and MPO by 60%. These effects were associated with reduced recruitment of neutrophils to the joint. The anti‑inflammatory effects of IL‑37 treatment were confirmed in SCW‑induced peritonitis, and shown to require the IL‑1 family decoy receptor IL‑1R8/SIGIRR. In IL‑37tg mice, synovial expression of IL‑37 reached peak levels during the resolution phase of the arthritis, and was associated with a reduction of joint swelling.

Conclusion: IL‑37 emerges as a key suppressor of joint and systemic inflammation. These findings demonstrate a role of IL‑37 in the pathogenesis of arthritis, and indicate a potential for IL‑37 in the treatment of rheumatoid arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treating-experimental-arthritis-with-the-innate-immune-inhibitor-il-37-reduces-joint-and-systemic-inflammation/