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.