Beneficial Effects of Fever
It should be emphasized that fever is not an illness but is, in fact, a physiologic mechanism that has beneficial effects in fighting infection. Body temperature elevation in pyrogenic-mediated fevers, in contrast to hyperthermic states, rarely exceeds 5° F (2.5° C) above normal.
Although the severity of some viral infections is decreased at these temperatures, most pathogens are not affected by a modest rise in temperature. Studies on bacterial infections in fish, lizards, rabbits, and humans, however, have shown an increase in survival correlated with the presence of fever.3,52-53 One well-studied effect of fever on bacterial proliferation is the effect of hypoferremia. Bacteria, which require iron for multiplication, are inhibited by the reduced availability of iron during the acute phase reaction. This response is augmented by the increased susceptibility of bacteria to low iron at higher temperatures.54-55 Certain neoplastic cells are inhibited during fever, although it is likely that inhibition of neoplastic cell division results from augmentation of immune responses.56Literature on the effect of fever is conflicting owing to the multiple variables present in in vivo studies and the application of heat in temperature ranges exceeding those of natural fevers in in vitro studies. Enhancement of host defenses, however, appears to be the primary beneficial effect of fever. Fever or heat applied in in vitro studies within the physiologic range of natural fevers has a beneficial effect on multiple processes of the adaptive immune response. Neutrophils and monocytes have increased motility and emigration, enhanced phagocytosis, increased oxygen radical production, and enhanced killing of intracellular bacteria. IFN production increases, and its antiviral, antitumor, antiproliferative, and natural killer (NK) cellstimulating properties are enhanced.
Increased T-cell proliferative responses to nonspecific mitogens IL-1 and IL-2 and enhanced T-helper cell activation, expression, recruitment, and cytotoxicity have all been correlated with fever. Enhancement of B cells, with a subsequent increase in production of antibodies, and enhanced expression of Fc receptors occur during fever.57Activity of pyrogenic cytokines is also influenced by temperatures achieved during fever. For example, in a mouseendotoxin model, fever enhanced the early expression of TNF-α but limited the duration of its expression. Production of IL-1β was delayed, whereas that of IL-6 (which downregulates production of TNF-α and IL-1β) was enhanced, preventing the simultaneous expression of TNF-α and IL-1β and the potential harmful effects of their simultaneous expression.58 Other studies have demonstrated that the effect of fever on various cytokines is specific for each cytokine and specific to body compartments. Thus fever is an important component of the coordinated and specific cytokine response of the host to various inflammatory 34557
stimuli.3,45,57