Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins

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Abstract
To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1.alpha. (IL-1), and prostaglandin E2 and F2.alpha. (PGE2 and PGF2.alpha.). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2.alpha. had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2.alpha. and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.