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Delineation of the Proinflammatory Cytokine Cascade in Fever Induction a
Author(s) -
ZETTERSTRÖM MARIA,
SUNDGRENANDERSSON ANNA K.,
ÖSTLUND PERNILLA,
BARTFAI TAMAS
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb08311.x
Subject(s) - proinflammatory cytokine , cascade , cytokine , interleukin 18 , virology , medicine , immunology , chemistry , inflammation , chromatography
Bacterial lipopolypolysaccharide (LPS)‐induced fever involves induction of the proinflammatory cytokines interleukin (IL)‐1α, IL‐1β, tumor necrosis factor‐α (TNF‐α), and IL‐6, both in the periphery and in the brain. These molecules can induce expression of each other and also regulate expression of their own receptors in a complex manner. The functional hierarchy of these highly inducible proteins is therefore difficult to determine. Using mice strains carrying the null mutations of IL‐1β, IL‐1RI, IL‐1RAcP, or IL‐6, respectively, we show that LPS‐induced fever involves IL‐1β, which acts at a complex consisting of the type I IL‐1 receptor and the IL‐1RAcP. This action occurs prior to central IL‐6 release, which has been shown to be a necessary component of fever responses induced by LPS, IL‐1β, and also TNF‐α. In the absence of IL‐1β, as in IL‐1β‐deficient mice, LPS, IL‐1α, and IL‐1β cause hyperresponsive fevers when exogenously applied. Murine TNF‐α is a poor pyrogen in mice even when mice are kept at thermoneutral temperature (30°C). TNF‐α‐mediated fever depends on central IL‐6 expression.