THE SEARCH FOR AN ENDOGENOUS ACTIVATOR

  • 1 January 1985
    • journal article
    • research article
    • Vol. 58  (2) , 153-163
Abstract
Certain febrile diseases are unaccompanied by infection or apparent hypersensitivity. In myocardial infarction or pulmonary embolism, fever was attributed to inflammation and/or tissue necrosis. Exogenous (microbial) pyrogens stimulate human and animal monocytes/macrophages to produce endogenous pyrogen (EP) in vitro. To determine if plasma and cellular endogenous mediators (EM) of inflammation induced EP production, human mononuclear cells (M/L) were incubated for 18 h with varying amounts of EM and the supernates assayed for EP in rabbits. Neutrophils (PMN), which do not generate EP and yet are a feature of acute inflammation, were tested. Neither viable, phorbol myristic acetate-stimulated PMN nor sonicated PMN, red blood cells or M/L stimulated human monocytes to produce EP. Human C3b and C5a, which mediate phagocytosis and chemotaxis, respectively, were also inactive. Despite its chemoattractant properties, the synthetic peptide FMLP [N-formyl-methionyl-leucyl-phenylalanine] failed to induce EP release. Since Poly I:Poly C (PIC; a synthetic, double-stranded RNA) is a potent pyrogen in rabbits, PIC was investigated as well as a native, single-stranded RNA (from Escherichia coli) and DNA (from calf thymus). None was active in vitro and only PIC caused fever when given to rabbits i.v. An endogenous activator of EP from human monocytes was found to explain fevers associated with inflammation alone.

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