The biology of interleukin 1 and comparison to tumor necrosis factor

Interleukin 1 (IL-1) is a major product of the stimulated monocyte and is responsible for diverse biological effects. The systemic effects of IL-1 include fever, increased circulating neutrophils, hepatic acute phase proteins, slow wave sleep, elevated insulin levels and hypotension. In vitro, IL-1 induces increased synthesis of a number of lymphokines (IL-2, IL-3, IL-4 and IL-6), a variety of colony stimulating factors, and endothelial factors leading to clot formation and vascular congestion. IL-1 also induces histamine release and granule release from basophils, eosinophils and neutrophils. IL-1 dramatically increases arachidonic acid metabolites in a variety of cells; increased PGE2 synthesis accounts for its inflammatory properties. Tumor necrosis factor shares with IL-1 many of the systemic and local effects of IL-1; these include fever, acute phase protein synthesis and sleep. Some of the in vitro effects of IL-1 are not shared with TNF, but the combination of TNF with IL-1 often enhances the response several-fold. A dramatic synergism between IL-1 and TNF occurs on islets of Langerhans. In vivo, these two cytokines induce shock and pulmonary hemorrhage when given together but at doses at which neither cytokine is effective alone. Profound leukopenia and thromocytopenia are present. Since both cytokines are produced in large amounts following appropriate stimulation, the end result for the host is the combined effect of both cytokines.