Studies on the pathogenesis of fever. II. Characterization of fever-producing substances from polymorphonuclear leukocytes and from the fluid of sterile exudates

Abstract

Further studies on fever production by injection of leukocyte extracts or cell-free supernatant fluids from peritoneal exudates in rabbits are reported. Granulocytes collected from peripheral blood or from pleural exudates contain a heat-labile pyrogenic substance. The material in extracts of leukocytes and in peritoneal fluids, which causes fever, is destroyed by heating for 30 minutes at 90 degrees C. at pH 7.2 and at 70 degrees C. at pH 4.5. It is active in producing fever over a pH range of 2.0 to 10.5 and maintains potency for as long as 6 months at 4 degrees C. The fever-producing substance in leukocyte extracts is not dialyzable. Its activity is not destroyed by trypsin, chymotrypsin, or ribonuclease. No evidence of plasma activator or inhibitor was detected. Significant temperature elevation in the rabbit was effected by a quantity of leukocyte extract containing 0.76 mg. protein and 0.054 mg. polysaccharide. The febrile response produced by the material under study was compared with that of Menkin's pyrexin as well as with that of bacterial pyrogens. Several significant differences were noted. The properties of pyrexin are similar to those of bacterial pyrogens. Amidopyrine suppressed the febrile response to injection of leukocyte extracts, whereas neither amidopyrine nor cortisone influenced the appearance of pyrogenic material in induced peritoneal exudates. Peritoneal fluids collected from rabbits made leukopenic by HN(2) were found to contain a fever-promoting substance. Its character has yet to be determined. It is concluded that there is present in polymorphonuclear leukocytes of rabbits a heat-labile factor capable of producing fever in rabbits and that the leukocyte is probably not the only source of such a factor.