Interleukin-1

For the past 30 years, considerable experimentation on the mechanisms of host responses to infection has centered on soluble products derived from phagocytic cells. The biologic activities of some of these products include fever mediated by endogenous pyrogen (EP) and induction of acute-phase responses by leukocytic endogenous mediator (LEM), EP and LEM have been characterized and purified and appear to be closely related, if not identical, molecules. Lymphocyte-activating factor (LAF), a recently described polypeptide that acts on lymphocytes, shares many of the physical properties of EP and LEM; when incubated with lymphocytes, purified EP/LEM is indistinguishable from LAF. The term interleukin-1 (IL-1) is now used to describe LAF, EP, and LEM as a single molecule or as a family of closely related molecules, although at present there is no known sequence analysis of EP, LEM, or LAF. In this review, experimental and clinical data are presented that link mediation of host responses to infection and inflammation to the production and activity of IL-1. Cell sources and inducers of IL-1 are discussed, as are its chemical nature and mechanisms of action. In addition, the importance of IL-1 and its effects on host defense mechanisms are presented. For example, how IL-1-mediated responses, such as elevated temperature, lymphocyte activation, and systemic metabolic changes, alter the host as well as the invading microbe are considered. The conclusions of this review are (1) that IL-1 is a key mediator of host responses to microbial invasion, (2) that IL-1 represents a true hormone produced during infection and inflammation, and (3) that its biologic activities account for several aspects of the acute-phase reaction.