The molecular stimulus for resetting of the hypothalamic set point for temperature has been partly elucidated for some infective and inflammatory states.
Bacterial proteins, particularly lipopolysaccharides, upon phagocytosis by cells of the mononuclear phagocytic system, cause release of an endogenous pyrogen molecule from the phagocyte, interleukin-1. Alternatively, inflammatory cells may release interleukin-1 and 6 in response to generalised inflammation.
These cytokines pass haematogenously to the preoptic area of the hypothalamus. At this site, there is thought to be an intermediate molecule which is stimulated by the cytokine to cause pyrexia. This was believed to be a prostaglandin due to the action of aspirin in reducing fever; evidence is equivocal.
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