THE PATHOGENESIS OF FEVER AND ITS THERAPEUTIC IMPLICATIONS

Physiologically, body temperature is adjusted to about 37 degrees C an d fever represents an elevation of this basal temperature above the no rmal range. The thermoregulatory centre located in the hypothalamus ma intains physiological temperature, while fever depends on the producti on of exogenous pyrogens, which induce biochemical modifications in th e hypothalamus. Exogenous pyrogens comprise lipopolysaccharides from G ram-negative bacteria and various toxins from Gram-positive organisms. These pyrogens can induce the release of endogenous pyrogens or cytok ines (CKs), e.g. interleukin (IL)-1, IL-6 and tumour necrosis factor ( TNF)-alpha. This in turn, leads to the production of prostaglandins (P Gs) of the E series. Afterwards, PGE(2) provokes stimulation of the ne urons localized within the hypothalamus, thereby triggering a reaction which culminates in the generation of fever. Besides bacterial infect ions, other conditions associated with fever, such as inflammatory bow el diseases, acquired immunodeficiency syndrome and autoimmune disease s, are characterized by the production of pyrogenic CKs. Therapeutical ly, besides conventional treatments of fever with antibiotics, cycloox ygenase inhibitors, non-steroidal and steroidal drugs and immunosuppre ssive drugs, novel therapeutic approaches are based on the experimenta l administration of anti-CK antibodies, IL-1 and TNF receptor antagoni sts and anti-inflammatory CKs (e. g. IL-10 and IL-13), respectively. ( C) 1998 Chapman & Hall Ltd.