An update on human interleukin-1: From molecular biology to clinical relevance

Abstract

Interleukin-1 (IL-1) represents a family of polypeptides with a wide range of biological activities. At least two dissimilar gene products have been cloned; there are probably more. The human IL-1 family plays an important role in the pathogenesis of many diseases and functions as a key mediator of the host response to various infectious, inflammatory, and immunologic challenges. Recombinant mouse (pI 5) and recombinant human (pI 7) IL-1's are being used to confirm the multiple biological properties of IL-1's but considerable investigation is required before the specific activities (biological units per milligram of protein) are established for each human IL-1 form. Some IL-1 biological activities such as the induction of hepatic acute-phase protein synthesis have been demonstrated in invertebrates predating the evolution of lymphocytes. IL-1 is highly inflammatory and increases the concentration of metabolites of arachidonic acid, most notably prostaglandin E₂, in brain, muscle, chondrocytes, and synovial fibroblasts. The synthesis of leukotrienes also is involved in the mechanism of its action on certain tissues. The cloning and expression of human IL-1 genes will expand our understanding of IL-1 in various diseases through improved detection systems and the use of cDNA probes; the development of IL-1 antagonists, as well as the use of IL-1 as an immunomodulator, is presently being considered.