Treating Experimental Arthritis with the Innate Immune Inhibitor Interleukin-37 Reduces Joint and Systemic Inflammation
IL-37, a member of the IL-1 family, has recently been characterised as a fundamental inhibitor of innate inflammation. This study examines the effects of recombinant IL-37 on joint inflammation and pathology in a mouse model of arthritis, and also explores its potential in the treatment of human joint inflammation.
In this mouse model of experimental arthritis, short-term, low-dose treatment with IL-37 suppressed joint and systemic inflammation. Wild-type mice received three intraperitoneal doses of IL-37 (1 µg per mouse), or human serum albumin as vehicle control, 24-, 12, and 2 hours before streptococcal cell wall induction of arthritis (intra-articular injection) or peritonitis (peritoneal injection).
IL-37-treated mice exhibited a 51.7% reduction in the severity of arthritis compared with vehicle-treated mice (P<0.01). However, treatment with IL-37 in IL-1R8-deficient mice did not reduce synovial cytokine levels or improve joint inflammation or swelling, suggesting that the IL-1R8 receptor is required for IL-37 to have its anti-inflammatory effect.
Examination of IL-37 and IL-1R8 gene expression in the synovia of patients with RA showed that ILR-1R8 expression but not IL-37 is increased. This presents an opportunity for therapeutic use of exogenous IL-37 in human joint inflammation.
This study demonstrates a rationale for using recombinant IL-37 in the treatment of arthritis.