interleukin36

Interleukin‑36 (IL‑36) refers to a sub‑family of cytokines within the interleukin‑1 superfamily that is involved in inflammatory and immune responses. The group is composed of three agonist members, IL‑36α, IL‑36β and IL‑36γ, as well as a natural antagonist, IL‑36Ra, and two additional receptor antagonists, IL‑38 and IL‑37, which modulate the activity of the agonists. All IL‑36 cytokines are produced as inactive precursors that must be cleaved by neutrophil elastase, cathepsin G or proteinase 3 to become biologically active. The mature cytokines exert their effects by binding to a complex of IL‑1 receptor–like 2 (IL‑1RL2) and IL‑1 receptor accessory protein (IL‑1RAcP), initiating downstream signalling pathways that include MAP kinase, NF‑κB and JAK/STAT activation.

IL‑36 signalling promotes the recruitment of immune cells such as neutrophils, macrophages and dendritic cells to sites of inflammation. It also enhances the expression of chemokines like CXCL1, CXCL8 and CCL20, thereby amplifying inflammatory cascades. The cytokine family has been implicated in skin disorders, especially psoriasis, where overexpression of IL‑36α, IL‑36γ and reduced IL‑36Ra levels correlate with disease severity. Additional associations have been identified with inflammatory bowel disease, rheumatoid arthritis, atopic dermatitis and systemic lupus erythematosus, suggesting a broad role in both innate and adaptive immunity.

Research has explored therapeutic targeting of IL‑36 signalling. Neutralizing antibodies against IL‑36 receptor and small molecule inhibitors of downstream kinases are under investigation in clinical trials for psoriasis and other inflammatory conditions. Genetic polymorphisms in the IL‑36 gene cluster have been linked to variations in disease susceptibility and response to therapy, underscoring the clinical relevance of this cytokine family.