STUDIES ON THE PATHOGENESIS OF FEVER

Abstract

The clearance of intravenously injected typhoid vaccine was studied in unsensitized, sensitized, and pyrogen-tolerant rabbits by passive transfer. The blood of unsensitized rabbits (not previously exposed to bacterial pyrogen) remained pyrogenic for normal recipients for 2 hours following the injection. In contrast, rabbits sensitized by 1 or 2 injections of the vaccine at least 3 weeks previously cleared their blood of the test vaccine within 1/2 hour, despite the fact that they exhibit the same febrile response as unsensitized rabbits. After 1 hour, however, a transferable pyrogenic substance was again demonstrable in the sera of this group. This newly appearing substance may be endogenous and may be the factor which directly affects the thermoregulatory centers of the brain. Rabbits made tolerant by repeated daily injections of vaccine have little febrile response. The blood of such animals cleared the injected vaccine within 5 minutes, and sera obtained 1 and 2 hours after the injection contained no secondary pyrogen.