The pyrogenic and mitogenic actions of interleukin-1 are related

Abstract

Our present understanding of the pathogenesis of fever is that host macrophages, following activation by an appropriate stimulus^1,2 such as Gram-negative lipopolysaccharide (LPS)³ immune complexes⁴, or primed lymphocytes in the presence of specific antigen⁵, synthesize and release endogenous pyrogen (EP). EP is carried in the blood circulation to the hypothalamic area of the brain where its action, involving a protein synthetic step⁶, results in an increase of the level at which body temperature is maintained⁷. Recently, it was shown^8,9 that EP is very similar and possibly identical to another macrophage mediator previously called lymphocyte activating factor and now known as interleukin-1 (IL-1)¹⁰ which, in conjunction with lectin¹¹ or specific antigen¹², induces clonal expansion of T lymphocytes. We show here that murine T-cell proliferation in response to IL-1 in vitro is greatly increased when the cells are exposed to a temperature typical of fever and that injection of the same IL-1 causes fever in mice. If this relationship exists in vivo, the resulting facilitation of a T-cell-dependent immune response may well confer survival value and contribute to the evolutionary conservation of fever—a phylogenetically ancient response to infection.