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Pathogenesis of Fever: Are Circulating Pyrogenic Cytokines the Only Mediators?

1998; Oxford University Press; Volume: 26; Issue: 6 Linguagem: Inglês

10.1086/516341

1537-6591

Mihai G. Netea, Bart Jan Kullberg, J.W.M. van der Meer,

Thermal Regulation in Medicine

cytokines may also take place at the level of the OVLT, where Pathogenesis of Fever: Are Circulating Pyrogenic monocytes that have been stimulated elsewhere may adhere to Cytokines the Only Mediators?endothelial cells and release cytokines, or where production of pyrogenic mediators by endothelial cells may be triggered by exogenous pyrogens.Alternatively, cell-associated forms of proin-SIR-We read with great interest the paper by Mackowiak et al.flammatory cytokines, rather than circulating cytokines, may stim-[1], which reviews recent advances in the understanding of the ulate brain microvascular cells and induce febrile responses.febrile response [1].In the section, ''The Pyrogenic Cytokines,''The pathways described above may explain the absence of circu-Hasday and Goldblum describe the now-classic model of the lating cytokines during many febrile conditions.Circulating cytopathogenesis of fever, in which circulating pyrogenic cytokines kines that act as pyrogens are probably responsible for fever in are believed to play a central role.In this model, exogenous pyroseverely ill patients with septic shock, whereas in patients with gens, such as bacterial toxins, stimulate monocytes/macrophages more moderate or mild infections, it is likely that other pathways and T lymphocytes to produce pyrogenic cytokines such as IL-1, are involved.Moreover, it is possible that more mechanisms are TNF-a, IL-6, and interferons.The circulating cytokines reach the involved in the induction of fever in certain situations.CNS, pass through fenestrated capillaries in the organum vasculosum of the lamina terminalis (OVLT) [2, 3], and stimulate the Mihai G. Netea, Bart-Jan Kullberg, synthesis of prostaglandin (PG) E 2 .PGE 2 activates the coordinated and Jos W.M. van der Meer endocrine, autonomic, and behavioral responses that lead to fever