Fever and acute phase response induced in rabbits by human recombinant interferon-gamma.
1. Intravenous (I.V.) and intracerebroventricular (I.C.V.) injections of human recombinant interferon-gamma (IFN-gamma) produced dose-dependent fevers in rabbits. The fever induced by I.V. injection was monophasic and the maximum elevation occurred 80-110 min after injection. The fever induced by I.C.V. injection was observed from about 20 min after injection and was remarkably prolonged over 4 h. 2. The development of pyrogenic tolerance to IFN-gamma was observed when rabbits were given I.V. injections on 3 successive days. Furthermore, the pyrogenicity of IFN-gamma was significantly attenuated by heating at 60 degrees C for 40 min. The I.V. injection of IFN-gamma enhanced the febrile response induced by endotoxin but had no effect on that induced by endogenous pyrogen. 3. The I.V. injection of a large dose of IFN-gamma (6 x 10(6) units/kg) induced an acute phase response, which included a reduction in plasma concentration of iron and zinc. 4. The present results suggest that IFN-gamma released from lymphocytes is one of the endogenous mediator proteins responsible for producing fever and acute phase response.