IL1s

IL-1s, or interleukin-1 family cytokines, are a group of structurally related proteins that coordinate inflammatory and immune responses. The best-characterized members are IL-1α and IL-1β, which are pro-inflammatory, and the endogenous antagonist IL-1 receptor antagonist (IL-1Ra). The family also includes other cytokines such as IL-18, IL-33, and members of the IL-36 subfamily.

IL-1α is typically active as a precursor and can function locally at sites of cell injury, whereas IL-1β is synthesized as an inactive pro-form and requires processing by caspase-1 within the inflammasome to become mature and secreted. IL-1Ra binds the IL-1 receptor without signaling, thereby blocking IL-1 activity. IL-1R2 can act as a decoy receptor that limits signaling. The signaling receptor complex commonly involves IL-1 receptor type I (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP).

Upon binding, these receptors recruit adaptor proteins such as MyD88 and activate downstream pathways including NF-κB and MAP kinases, leading to the expression of inflammatory genes. IL-1 induces fever and the production of acute-phase proteins, promotes leukocyte recruitment, and enhances expression of adhesion molecules.

Clinically, dysregulation of IL-1 signaling is associated with autoinflammatory and autoimmune diseases, including cryopyrin-associated periodic syndromes, systemic juvenile idiopathic arthritis, and gout. Therapeutic strategies include IL-1 blockade with anakinra (recombinant IL-1Ra), canakinumab (neutralizing IL-1β antibody), and rilonacept (a soluble decoy receptor).

Beyond IL-1α and IL-1β, the IL-1 family comprises several other ligands with diverse roles in immunity, inflammation, and tissue homeostasis, illustrating the breadth of this cytokine pathway in health and disease.