THE PRODUCTION OF FEVER BY INFLUENZAL VIRUSES : II. TOLERANCE IN RABBITS TO THE PYROGENIC EFFECT OF INFLUENZAL VIRUSES

The mechanism of the fever caused by the intravenous injection of viruses of the influenza group in rabbits has been studied by observing the effect of repeated injections of the same or heterologous viruses. An initial injection of the PR8 strain of influenza A, the Lee strain of influenza B, or the "B" strain of NDV conferred tolerance to the pyrogenic effect of homologous virus administered on the following day. The period of tolerance lasted approximately 11 days. Prior injection of virus appeared also to protect against the lymphopenic action of homologous strains. These viruses were found to confer tolerance to the fever-producing effect of heterologous strains in an order corresponding to their positions in the receptor gradient of Burnet. Heated virus preparations appeared to confer tolerance in proportion to survival of hemagglutinin. Tolerance is probably unrelated to specific antibody formation since it is lost during a period of rapid immune response and heterologous strains exert a protective effect. No cross-tolerance was demonstrable between viruses and bacterial pyrogens and reticulo-endothelial blockade with thorotrast failed to modify the unresponsiveness of animals to 2nd day injections of homologous virus. Prevention of fever with antipyrine did not interfere with the protective effect of initial injections of virus. Arguments for and against a hypothesis that union of the virus particle with a receptor substance may play a part in the production of fever by these viruses are discussed.