IL37 is a novel anti-inflammatory cytokine of the IL-1 family that suppresses innate immune and inflammatory responses. 1 IL37 functions through dual mechanisms: intracellularly via nuclear translocation involving SMAD3, where it regulates transcription, and extracellularly after secretion, binding to the IL-18 receptor alpha chain in association with the co-receptor IL-18RAP. 12 IL37 acts as a brake on inflammation by reducing pro-inflammatory cytokine production including IL-1β, IL-6, and TNF-α while sparing anti-inflammatory mediators. 13 In human monocytes deficient in IL-37, LPS and IL-1β-induced cytokines increase 2-3 fold, demonstrating IL37's critical suppressive role. 1 IL37 shows therapeutic potential across multiple disease contexts: it reduces inflammation in models of LPS shock, chemical colitis, and contact dermatitis, 1 and dampens cartilage degradation in osteoarthritis by inhibiting matrix-degrading enzymes. 3 Recent evidence demonstrates IL-37-producing regulatory B cells exhibit superior anti-inflammatory efficacy in psoriasis and colitis models. 4 Circulating IL-37 declines with aging and inversely correlates with chr2 inflammation markers, suggesting relevance to healthspan. 5 These findings support IL37 as a potential therapeutic target for inflammatory and autoimmune diseases.