Interleukin-37 (IL-37)

Interleukin-37 (IL-37) is an anti-inflammatory cytokine belonging to the interleukin-1 family, encoded by the *IL-37* gene located on chromosome 2 in humans[1][3][4]. It primarily functions to suppress excessive immune responses—with both intracellular and extracellular actions—by inhibiting pro-inflammatory cytokine production and limiting the progression of various inflammatory and autoimmune diseases. The mature protein is activated via caspase-1 cleavage and engages in signaling through binding to IL-18 receptor α (IL-18Rα) and the decoy receptor IL-1R8, decoying downstream MyD88, and limiting inflammatory signaling. Intracellular IL-37 binds Smad3, allowing nuclear translocation and suppression of cytokine gene expression. IL-37 is expressed in diverse immune and non-immune tissues, with the b isoform being the most biologically active[1][3][4]. It has roles in cancer modulation, age-associated immunosenescence, and tissue protection from inflammatory damage. Its levels are altered in diseases such as cancers and inflammatory conditions, making it a potential therapeutic target and biomarker[1][4]. No drugs specifically target IL-37 as of 2025, but its broad immunosuppressive capacity poses safety concerns regarding infection and immune regulation.

Other names

Interleukin-1 family member 7IL1F7IL-1F7IL-1H4IL-1 zetaIL-1RP1FIL1ZInterleukin-1 homolog 4Interleukin-1-related protein

- Enhancement of anti-inflammatory signaling via IL-18 receptor α and IL-1 receptor 8 complex formation - Inhibition of pro-inflammatory cytokine gene transcription through binding/phosphorylation of Smad3 and nuclear translocation - Downregulation of NF-κB and MAPK pathways