Ivan L. Bennett

BENNETT, IVAN L. Jr. M.D.; CARY, FREEMAN H. M.D.; MITCHELL, GEORGE L. Jr. M.D.; COOPER, MANUEL N. M.D. Author Information

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.

From the Department of Medicine, Emory University Medical School, Atlanta, Georgia * Present address: Department of Medicine, Duke Hospital, Durham, North Carolina.

A CONSEQUENCE of the successful treatment of many bacterial diseases with antibiotics has been the attempt to prevent infection by the administration of these agents prophylactically. This approach has been strikingly effective in cases in which chemoprophylaxis has been directed at a single etiologic agent such as the beta-hemolytic streptococcus, the meningococcus, the gonococcus and some species of shigella. There is no doubt that impending outbreaks of infection by these organisms can be aborted by administration of the antimicrobial drugs. In addition to this specific use, antibiotics are frequently employed in attempts to prevent "secondary" bacterial complications of diseases in . . .

Injection of extracts or suspensions of various rabbit tissues was found to be without effect upon the body temperature of normal rabbits. Occasionally, extracts of bone marrow produced transient fever, and saline extracts of acute inflammatory lesions of the Shwartzman and Arthus types were found to produce fever when injected intravenously. Suspensions or extracts of polymorphonuclear leukocytes collected from sterile peritoneal exudates contain a heat-labile substance which produced fever whereas those of erythrocytes, macrophages, and lymphocytes failed to do so. The cell-free supernatant fluid of sterile peritoneal exudates obtained at the stage when polymorphonuclear leukocytes predominate also proved capable of producing fever.