NEUROBIOLOGICAL CONCEPTS OF FEVER GENERATION AND SUPPRESSION

Fever is induced by interactions of bacterial pyrogens with cells from the immune system, which subsequently release a cascade of cytokines. After intramuscular injection of lipopolysaccharide (LPS) from E. col i, increased amounts of tumor necrosis factor (TNF) and interleukin-6 (IL-6) can be measured in blood plasma and in perfusates of the anteri or hypothalamus, where body temperature is regulated. These substances are therefore candidates to be involved in the modification of thermo regulatory structures leading to the febrile rise in body temperature. This increase of body temperature is limited and sometimes even preve nted by the actions of endogenous antipyretic neuropeptides like argin ine vasopressin (AVP), adrenocorticotropin (ACTH) and melanocyte-stimu lating hormones (MSHs) liberated within the brain or systemically duri ng fever. For AVP, most experimental evidence confirms antipyretic pat hways from the hypothalamic paraventricular nucleus to the septal area of the limbic system, which are activated during fever and by several stressful stimuli. Fever and endogenous antipyresis are interconnecte d and result from interactions between the immune system and the centr al nervous system.