Production of fever in rabbits with extracts of tissue culture cells infected with Coxsackie virus.

Abstract

Abstract The following experiments describe the characteristics of the fever produced in rabbits by Coxsackie virus grown in monkey kidney cells. Viruses grown in tissue culture have not previously been shown to produce fever. The tissue culture system affords the advantage of excluding the possibility of contamination by leukocytic pyrogen which could conceivably occur in the chick embryo. Monkey kidney cells, either whole or disrupted, which had not been inoculated with virus failed to produce fever following injection into rabbits. Consistent fevers were produced, however, by aliquots of disrupted cells containing Coxsackie B-1 virus. The fever regularly followed a latent period of 45 minutes and produced 2 peaks, one at 90 minutes and one at 3 to 4 hours. Identical fevers were produced in rabbits previously made tolerant to the fever-producing effect of bacterial endotoxin. Rabbits injected on consecutive days with Coxsackie virus pyrogen exhibited tolerance by the third day. The pyrogenic activity was not diminished even though aliquots were heated to 70 °C. for 30 minutes, indicating that the fever is not due to active infection. These findings indicate that extracts of monkey kidney cells infected with Coxsackie virus in the absence of leukocytes produce a characteristic fever following intravenous injection into rabbits. Attempts to obtain similar results with adenovirus and vaccinia virus grown in HeLa cells were not successful.