The Interleukin-1 Family

Interleukin-1 (IL-1) was the first interleukin to be identified and characterized as a major endogenous pyrogen and a potent proinflammatory and pleiotropic molecule involved in resistance to microbes and in injury. Since IL-1's discovery, the IL-1 system has impressively grown and now its ligands and receptors are recognized as large and complex families of molecules involved in host responses in infections and inflammation, as well as in the activation of innate and adaptive cells. Indeed, all cells of the innate immune system express and/or are affected by IL-1 family members, and IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive cells.The IL-1 family includes ligands with agonist activity, receptor antagonists, and an anti-inflammatory cytokine. Members of the IL-1 receptor family include signaling receptor complexes, decoy receptors, and negative regulators. The IL-1 system is tightly controlled at different levels by antagonists, decoy receptors, scavengers, and dominant negative molecules. Indeed, the deregulated or excessive activation of the IL-1 system is the potential cause of dangerous and detrimental local or systemic inflammatory reactions, as well as autoimmune or allergic responses, and anti-IL-1 therapies have had a tremendous impact on inflammatory diseases.