[Fever in acute illness: beneficial or harmful?]

Fever has had a long phylogenetic history: it occurs not only in infected birds and mammals, but also in infected reptiles, amphibians, fish and even insects. When these "cold-blooded" animals are prevented from adapting their body temperature to the risen thermoregulatory set-point by behavioral means, a more severe state of disease and a higher mortality are the consequences. It seems unlikely that an energy-dependent process, such as fever, would have been retained for hundreds of millions of years, in so many groups of organisms, if it provided no selective advantage. Fever may represent a leukocyte-based amplification mechanism to affect host challenge: enhanced motility of leukocytes, enhanced lymphocyte response to mitogens, increased production of interferon, enhanced immune response to viral antigens. Evidence for a beneficial effect of fever is also supported by the results of our animal experiments. Intraperitoneal injection of a high dose of bacterial lipopolysaccharide (LPS) in rats induces a septic shock like state which is accompanied by hypothermia on the day of LPS-administration and a robust fever on the following days. Co-injection of a neutralizing synthetic form of the soluble tumor necrosis factor (TNF) type 1 receptor completely neutralizes LPS-induced bioactive TNF in the lavage of the abdominal cavity and in blood plasma. Treatment with the TNF-antagonist results in much faster recovery from the hypothermic state. The rats develop pronounced fever already on the day of injection and there is significantly less reduction in body weight and food and water intake. Similar, but less pronounced effects can be induced by treatment with inhibitors of the inducible form of nitric oxide (NO)-synthase indicating that TNF-induced detrimental effects are, in part, mediated by excessive formation of NO. These results confirm that an accelerated onset of fever or a faster recovery from hypothermia in a septic state may have rather beneficial than maladaptive effects.