Fever from pathogenic fungi.

Most studies of fever have dealt with the pyrogenic activity of the bacterial lipopolysaccharides of gram-negative bacteria (1). The pyrogenic properties of pathogenic gram-positive bacteria, on the other hand, have been the stubject of only a few reports. It is of interest, however, that intravenous injection of living staphylococci and corynebacteria were found to produce higher fever in rabbits than did gram-negative bacteria (2), and that pronounced elevations of body temperature were found after intravenous injections of both living and heat-killed streptococci, as well as streptococcal lysates (3). The pyrogenicity of another group of gram-positive microorganisms, the pathogenic fungi, has received no consideration in the literature, although Salvin (4) reported that they possess lethal endotoxins for mice. The following study was undertaken, therefore, to determine which of the common pathogenic fungi can induce fever and to compare their pyrogenic effect with that of the lipopolysaccharides of gramnegative bacteria. The presence of pyrogens in saprophytic molds has been reported but the characteristics of the pyrogen and of the fever response were not described (5). fer (pH 7.1) containinig NaH2PO4 1.6 g, Na2HPO4 7.5 g, and NaCl 4.4 g per L H2O, washed 3 times by centrifugatioin and suspended in 1.0 ml of the buffered saline to give the desired number of fungus cells. The fungus cells were enumerated in a Spencer bright line Neubauer hemocytometer couintinig chamber after dilution in saline in a red cell or white cell pipet. Pyrogeat stuidies. Living or autoclaved fungus suspensionis were injected into the marginal ear vein of rabbits and temperatures were measured rectally by insertinlg the glass probe of the thermistor apparatus (Sargent). Autoclaving of fungi was done at 1450 C for 15 minutes at 15 pounds pressure, and always sterilized the culture. Glassware and needles were rendered free of pyrogens by heating in an oven at 1700 C for 2 hours. Pyrogen-free solutionis of physiologic saline and water were purchased from the Abbott Company. Albino rabbits of both sexes, weighing 3 to 5 kg, were kept in an air-conditioned room at approximately 700 F. They were conditioned by measuring the temperatures hourly for 8 hours on the day preceding each experiment and animals were used only if their temperatures remained within a constanit range of plus or minus 0.30 F during the period of conditioninig. On the day of the experiment, temperatures were measured at 30-minute intervals for 2 hours before injectioni and hourly for 8 hours thereafter. Temperatures were also taken immediately before inj ection and 30 minutes afterward. Animals were rejected for the study if their temperatures were not constant during the preliminary period of 2 hours before injection.