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The pathogenesis and the adaptive value of fever

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Soszynski D.

Postępy Higieny i Medycyny Doświadczalnej

2003

vol. 57

issue 5

531-544

Fever is a part of the acute phase response to infection and inflammation. We now understand that fever is a complex physiological response that is aimed at facilitating survival of the host. The fever is induced by endogenous inflammatory mediators, such as prostaglandins and pyrogenic cytokines, that are released by immune cells activated by exogenous pyrogens. Although the pathways (humoral and/or neuronal) responsible for transfer of the pyretic signals from the blood to the brain are still under discussion, it is generally accepted that they act on the level of the anterior hypothalamus to raise the thermoregulatory set-point. Results of studies of the adaptive value of fever demonstrate an association between a rise in body temperature and a decrease in mortality and morbidity during infection. These data along with data from evolutionary studies provide a strong support for the concept that fever is a beneficial during infection in endotherms and ectotherms, vertebrates as well as in invertebrates. There are also evidence showing that fever may be used as a therapeutic tool, especially in cancer therapy. Based on the data reviewed in this article, it can be concluded that fever has evolved as a host defense mechanism which was preserved within the animal kingdom through hundreds of millions of years of evolution.

Mechanisms of development of tolerance to repeated injection of exogenous pyrogens

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Soszynski D.

Postępy Higieny i Medycyny Doświadczalnej

2000

vol. 54

issue 4

537-551

Pyrogenic tolerance has been recognized for many years in a variety of species although the mechanisms that are responsible for its development are not well understood. The development of pyrogenic tolerance is associated with the stepwise diminution of pathophysiological and behavioral responses induced by exogenous pyrogens, such as fever, reduction in food and water inteke. Several studies either in vivo or ex vivo have indicated the role of various proinflammatory cytokines in the development of pyrogenic tolerance. Most of these studies have indicated that pyrogenic tolerance is associated with down-regulation of cytokine production as well as their biological activity The mechanisms responsible for down-regulation of cytokine production during development of pyrogenic tolerance are unclear. Since glucocorticoids are required for induction of tolerance, it has been postulated that well known glucocorticoids-dependent negative feedback on the production and biological activity of cytokines may play an important role in development of pyrogenic tolerance. We can not, however, rule out possibility that other mechanisms may participate directly or indirectly in a suppression of cytokines response due to repeated exogenous pyrogen challenge. Either the enhanced uptake of exogenous pyrogens by the hepatic Kupffer cells or the desensitization to exogenous pyrogens by the loss of binding sites, have been proposed as an additional mechanisms which may participate in exogenous pyrogen hyporesponsiveness.

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2 Postępy Higieny i Medycyny Doświadczalnej

1 2003

1 2000

2 Soszynski D.

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The pathogenesis and the adaptive value of fever

Mechanisms of development of tolerance to repeated injection of exogenous pyrogens