Pathogenesis of Fever

#x203A; Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. › Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). › These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. › The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. › Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. › Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever. › The protective processes of the immune response are optimal at high temperature (around 39.5°C). › Not all effects resulting from fever generation benefit the host; some are harmful and even lethal. This occurs mainly by overproduction of the cytokines or imbalance between cytokines and their inhibitors, such as severe and fulminate infections and septic shock.