Pathogenesis of Fever
The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy.
Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.
The hypothalamic thermoregulatory centre accomplishes heat production by inducing shivering and heat conservation through vasoconstriction. At an established degree, fever is regulated (even at a temperature of over 41.0 °C) and heat production approximates loss, as in health, though at a higher level of the set point. Therefore fever does not climb up relentlessly.
In addition to the function as an endogenous pyrogen, IL-1 activates T-lymphocytes to produce various factors, such as INF and IL-2, which are vital for immune response. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.
The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the host’s survival during infection.
KeywordsExogenous and endogenous pyrogens Interleukins Interferons Tumour necrosis factors Thermoregulation