Interleukin-38 (IL-38)

Interleukin-38 (IL-38) is a cytokine within the interleukin-1 family, specifically part of the interleukin-36 subfamily, encoded by the IL1F10 gene on chromosome 2q13-14.1[1][3][4][5]. This protein is a 152-amino acid polypeptide (~17 kDa) structurally similar to the interleukin-1 receptor antagonist (IL-1Ra) and interleukin-36 receptor antagonist (IL-36Ra), sharing 37–43% sequence homology[1][3][5]. IL-38 is predominantly expressed in immune-related tissues such as skin, tonsil (B cells), spleen, and lower levels in non-immune tissues such as heart and placenta[2][3][4][5]. Biologically, IL-38 functions as an anti-inflammatory mediator, acting as a competitive antagonist at the IL-36 receptor (IL-36R), modulating the production of proinflammatory cytokines (notably IL-17, IL-22, and IL-8), and influencing the activity of Th17 and other immune cells[2][4][5][7]. IL-38 also binds to other members of the IL-1 receptor family, including IL-1RAPL1 (TIGIRR-2), where it inhibits JNK/AP1 pathway activity, contributing to the regulation of inflammatory responses[1][4][7]. Its dysregulation is implicated in autoimmune diseases, inflammatory diseases, and several neurological and cardiovascular disorders, suggesting a modulatory, protective role in various pathophysiological processes[4][5][6][7]. Therapeutic strategies targeting IL-38, or its pathway, are being explored for their anti-inflammatory and disease-modifying potential[4][5].

Other names

IL1F10IL-1 family member 10Interleukin-1 homolog 10IL-1HY2Interleukin-36 subfamily memberIL-1F10

Competitive antagonist of interleukin-36 receptor (IL-36R, also known as IL-1 receptor-related protein 2 or IL-1Rrp2). Binds to IL-1RAPL1 (TIGIRR-2), exerting anti-inflammatory actions by inhibiting JNK/AP1 pathway in macrophages. May also interact with IL-1 receptor type I (IL-1R1), inhibiting downstream inflammatory signaling.