Interleukin-1 and the effects of cyclooxygenase inhibitors on its biological activities

Abstract

Interleukin-1 (IL-1) is a polypeptide produced following infection, injury, or antigenic challenge. Although the macrophage is a primary source of IL-1, epidermal, epithelial, lymphoid, and vascular tissues synthesize IL-1. When IL-1 gains access to the circulation, it induces a broad spectrum of systemic changes in physiologic, neurologic, metabolic, hematologic, and endocrine systems. However, because IL-1 lacks a signal peptide, a considerable amount of the IL-1 synthesized may remain associated with the cell and particularly as part of the plasma membrane where it may participate in lymphocyte activation and mesenchymal tissue remodeling. Two gene products code for IL-1: IL-1-beta and IL-1-alpha. The spectrum of biological activities of IL-1 are induced by both forms and receptors for IL-1 recognize both forms. The most consistent property of IL-1 is upregulation of cellular metabolism and increased expression of several genes coding for biologically active molecules. IL-1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites, most consistently, prostaglandin E. IL-1 also acts synergistically with other cytokines, particularly tumor necrosis factor. Some of the multiple biological effects of IL-1 and tumor necrosis factor are prevented by cyclooxygenase inhibitors whereas others are unaffected. Given the widespread use of cyclooxygenase inhibitors, understanding their effect on IL-1 and tumor necrosis factor action is important in several disease models.