Autonomic and Endocrine Adjustments in Fever

Abstract

Fever is a symptom common to infectious diseases with bacteria and viruses, and it is also observed in experimental animals in response to the peripheral or central administration of lipopolysaccharide (LPS), the principal element of bacterial endotoxin. Studies on the experimental analysis of fever trying to clarify each step in the sequence from LPS injection to thermoregulatory effector responses, which produce an increase in body temperature, have a long history. In the investigations of the fever mechanism, knowledge especially about the intermediary molecules that participate in LPS fever is rapidly accumulating, and the list of substances considered as relevant now includes endogenous pyrogens, interferons, interleukin1 and -6, tumor necrosis factors, and prostaglandins. On the other hand, the results of research on fever suppression at full-term pregnancy have suggested that certain antipyretic substances, so-called endogenous cryogens, exist. As a candidate of endogenous cryogen, arginine-vasopressin, for instance, suppressed fever induced by pyrogen administration when the animals were pretreated with the cryogen. All pyrogens produce an increase in body temperature affecting the intracerebral thermoregulatory center; however, it is not yet known how and where those peripherally generated substances drive the central nervous mechanism located behind the blood-brain barrier. Recent reports suggest that neuronal signals relating to the generation of fever are probably transferred neuronally from the periphery to the brain, because subdiaphragmatic vagotomy suppresses fever caused by the peripheral administration of LPS. Therefore, fever as a host defense reaction may be considered as a regulated increase in the temperature based on the integration of a multitude of humoral and neuronal information. These inputs include drives for the rise in body temperature, but also opposing drives, probably generated secondarily, that ultimately maintain fever hyperthermia in the nondeleterious range.