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IL‐6 and IL‐1β in Fever: Studies Using Cytokine‐Deficient (Knockout) Mice a
Author(s) -
KOZAK WIESLAW,
KLUGER MATTHEW J.,
SOSZYNSKI DARIUSZ,
CONN CAROLE A.,
RUDOLPH KARIN,
LEON LISA R.,
ZHENG HUI
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.tb08310.x
Subject(s) - lipopolysaccharide , endocrinology , medicine , turpentine , tumor necrosis factor alpha , inflammation , cytokine , interleukin 6 , chemistry , interleukin , ratón , knockout mouse , immunology , receptor , organic chemistry
Previous data support the hypothesis that during inflammation, interleukin (IL)‐1β and IL‐6 are involved in fever, in activation of the hypothalamic‐pituitary‐adrenal (HPA) axis, and in the induction of eicosanoids. Most of the pathophysiologic effects of IL‐1β and IL‐6 are mediated by prostaglandins (PGs), modulated by other cytokines, and antagonized by glucocorticoids (GC), a final product of the HPA axis. To further test these relationships, we measured changes in body temperature using biotelemetry in mice deficient in genes for IL‐1β and/or IL‐6 (IL‐1β knockout [KO] and IL‐6 KO) following injection with lipopolysaccharide (LPS) to induce systemic inflammation or turpentine to induce local abscess. Circulating IL‐6, tumor necrosis factor a (TNF‐α), GC, and PGE 2 were measured in these mice after treatment. IL‐1β KO mice responded with reduced fever and IL‐6 KO mice with normal fever to a high dose of LPS. In contrast, neither type of KO mice produced fever to turpentine. PGE 2 levels (measured in the circulation) were suppressed in both types of KO mice injected with turpentine. IL‐1β KO mice showed deficiency in IL‐6 following turpentine, but not LPS, injection. LPS‐induced increases in TNF‐α did not differ between IL‐1β KO mice and their wild‐type counterparts, whereas IL‐6 KO mice showed exacerbated LPS‐induced circulating TNF‐α. No differences were noted in plasma elevations of GC between KO and wild‐type mice following injection of LPS or turpentine, indicating that IL‐1β and IL‐6 are not required for activation of the HPA axis during inflammation. Our data demonstrate that in the mouse, IL‐1β and IL‐6 are critical for the induction of fever during local inflammation, whereas in systemic inflammation they appear only to contribute to fever.