Studies on T H E Pathogenesis of Fever with Influenzal Viruses I. T~e Appearance O1' an Endogenous Pyrogen in the Blood following Intravenous Injection of Virus

Although there has been extensive study of various aspects of thermoregulation, the sequence of events which lead to the development of fever following the inoculation of pyrogenic agents has remained obscure. Most investigations of the pathogenesis of fever have been carried out with bacterial endotoxins. These agents are potent toxins and in minute dosages produce cellular damage and a variety d pharmacological effects in addition to fever (1-3). A widely held hypothesis is that endotoxins act indirectly in the pathogenesis of fever by the liberation in the host of some pyrogenic product of tissue injury (4). This substance, in turn, presumably stimulates the thermoregulatory centers directly to cause fever. Although there is an obvious clinical correlation between the presence of inflammation and fever, there has been little experimental evidence for the role of such postulated endogenous substances in the development of the febrile response.