Pyrogenicity of Influenza Virus in Rabbits. ∗

Abstract

During an investigation of the toxicity of influenza virus in rabbits, it was noted that the intravenous injection of infected chorio-allantoic fluid was followed by fever. To study this phenomenon, animals were placed in individual stalls, 3 preliminary rectal temperatures were taken at 30-minute intervals to establish a baseline, and the virus preparation to be tested was then injected into the marginal ear-vein. Rectal temperatures were recorded every 30 minutes throughout an observation period of 6 hours after injection. All glassware and saline solutions used were uncontaminated with bacterial pyrogens. A single pool of chorio-allantoic fluid from embryos infected with the PR-8 strain, having a hemagglutinin titer of 1:1024, 1 was used.

One ml of this material consistently caused a rise in temperature beginning l 1/2 to 2 hours after injection, reaching a peak of 3-4°F above the baseline in the next 4 hours, and gradually falling to normal. Although doses as small as 0.025 ml produced fever, the increases in temperature were of a lower order.

Normal chorio-allantoic fluid and infected fluid from which the virus particles had been removed by centrifugation at 30,000 R.P.M. or by adsorption on chicken erythrocytes gave no fever. The virus resuspended in normal saline solution produced typical temperature elevations.

No fever followed the injection of PR-8 virus neutralized with homologous immune serum.

The febrile response in rabbits is independent of the infectivity of the virus but seems to be related to its adsorptive capacity. Heating at 56°C for 30 minutes destroyed the infectivity of PR-8 for chick embryos but a portion of the hemagglutinin was retained (1024 to 128); this material produced definite fever in rabbits. Heating at 62°C for 30 minutes destroyed the hemagglutinin titer and these preparations were then non-pyrogenic.