Comprehensive biology of antipyretic pathways

Pyrogens, the fever inducing substances accidently enter into a human body through contamination from medical or pharmaceutical products may create mild to severe complications including septicaemia and shocking syndromes. To avoid such drastic situations all the pharmaceuticals and medical devices are analysed for presence of pyrogens prior to their release into market. The entry of exogenous pyrogens like bacterial endotoxins induces the release of endogenous pyrogens or inflammatory cytokines that activate immune system to defend against these pathogens. Generation of heat is considered as one of the important defence mechanism of body achieved through receptor mediated interaction of endogenous pyrogens at the thermoregulatory centre of hypothalamus. However, uncontrolled fever and febrile reaction may cause lethal effects to the subject itself. So a well sophistically functioning antipyretic mechanism is necessary to achieve thermoregulation. The coordinated interaction of antipyretic cytokines and other mediators are active in human immune system which play a crucial role in maintaining thermal homeostasis. The multiple interacting antipyretic signals and their mechanism are the major subjects of this review.