Interleukin-38
Interleukin-38 (IL-38) is a small protein in the IL-1 family that helps regulate inflammation and the body’s defense. In humans it’s called IL-1F10 and shares a similar shape to the IL-1 receptor antagonist. The IL-38 gene sits on chromosome 2q13 and the protein is made by many cells in several tissues, especially skin, tonsil B cells, spleen, thymus, heart, placenta, and fetal liver. IL-38 helps tune both innate and adaptive immune responses.
IL-38 likely comes from an ancient IL-1RN gene and is about 41% similar to IL-1Ra and 43% to IL-36Ra. Its levels can change in diseases such as ankylosing spondylitis, cardiovascular disease, rheumatoid arthritis, and hidradenitis suppurativa. The protein is thought to be produced in shorter forms after processing, with a predicted 3-152 amino acid form being active; the exact processing enzyme and the body’s natural variant are still unknown. The 20-152 amino acid form appears more active in some contexts. IL-38 binds to the IL-36 receptor (IL-36R) and can have a varied, non-linear effect on inflammation depending on concentration and processing. It may also interact with TIGIRR-2 (IL-1RAPL1) and act as an antagonist in certain inflammatory pathways.
Key points
- IL-38 can both block and promote inflammatory signals, depending on context and form.
- It is linked to several inflammatory and autoimmune diseases, including lupus, Sjögren’s disease, and rheumatoid arthritis.
- In animal models, higher IL-38 often reduces disease symptoms and inflammatory markers like IL-17 and TNF.
- IL-38 is a potential target for therapies aiming to treat inflammatory conditions, though its exact roles and best therapeutic form remain under investigation.
This page was last edited on 2 February 2026, at 23:57 (CET).