Fever: Causes and consequences

The present review distinguishes pathogenic, neurogenic, and psychogenic fever, but focuses largely on pathogenic fever, the hallmark of infectious disease. The data presented show that a complex cascade of events underlies pathogenic fever, which in broad outline — and with frank disregard of contradictory data — can be described as follows. An invading microorganism releases endotoxin that stimulates macrophages to synthesize a variety of pyrogenic compounds called cytokines. Carried in blood, these cytokines reach the perivascular spaces of the organum vasculosum laminae terminalis (OVLT) and other regions near the brain where they promote the synthesis and release of prostaglandin (PGE 2). This prostaglandin then penetrates the blood-brain barrier to evoke the autonomic and behavioral responses characteristic of fever. But then once expressed, fever does not continue unchecked; endogenous antipyretics likely act on the septum to limit the rise in body temperature. The present review also examines fever-resistance in neonates, the blunting of fever in the aged, and the behaviorally induced rise in body temperature following infection in ectotherms. And finally it takes up the question of whether fever enhances immune responsiveness, and through such enhancement contributes to host survival.