Corticosterone Modulates Interleukin-Evoked Fever in the Rat

Abstract

The role of endogenous corticoids in fever responses caused by recombinant murine interleukin (IL)-1β and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after intracerebroven-tricular (icv) injection of these ILs and lowered body temperature. Intraperitoneal administration of the same doses of ILs did not produce fever in intact animals or hypothermia in adrenalectomized rats, thus suggesting a central site of action of IL-1β and IL-6 in these experiments. Chronic replacement with moderate doses of corticosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1β but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated with corticosterone and thereafter with either IL-1β or IL-6 developed fever more rapidly than did chronically corticosterone-treated animals. In intact animals corticosterone blocked the fever response to icv injected IL-1β. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central effect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probably reduce the magnitude of the fever response.

Expression of genes controlling transport and catabolism of prostaglandin E2in lipopolysaccharide fever

“…Because LPS is a potent stimulus for corticosteroid release (33), transcriptional downregulation of 15-PGDH during LPS fever may be triggered by endogenous glucocorticoids. Such an action of glucocorticoids would agree with their "permissive" role in febrile pathogenesis (1,56).…”

Endotoxin and Interleukin 1 Decrease the Affinity of Hippocampal Mineralocorticoid (Type I) Receptor in Parallel to Activation of the Hypothalamic-Pituitary-Adrenal Axis

“…During these pathophysiological conditions, the adrenal corticoids are believed to prevent an overshoot of inflammatory reactions [2] and to limit the magnitude of the fever response [3], Moreover, the steroids have a permissive effect on the hepatic acute phase reaction [4] and on the fever response [5], The acti vation of the hypothalamic-pituitary-adrenal (HPA) axis is triggered by products from microorganisms, such as peptidoglycans and lipopolysaccharides (LPS), which rap idly stimulate the synthesis of immunoregulatory mole cules, among them interleukin 1 (IL1), IL6 and tumor necrosis factor [ 1,[6][7][8]. These cytokines, in turn, evoke an immune stimulation as well as endocrine, metabolic and behavioral changes during illness [1,7].…”

Corticosterone Controls lnterleukin‐1β Expression and Sickness Behavior in the Rat

“…In this context the neuropeptides alpha melanocyte-stimulating hormone and arginin vasopressin were found as endogenous antagonists of pyrogens and probably also of sickness behavior-inducing substances (2,4,5 ) . The most potent antiinflammatory agents, however, are glucocorticoids, which may also downregulate fever (6)(7)(8) and some components of sickness behavior (9, 10; for a review see ref. 3).…”

“…Therefore adrenalectomized rats produce more IL-6 in peripheral tissues in response to LPS (16)(17)(18)(19) and develop higher fevers than adrenalintact animals ( 16,17,19). Administration of glucocorticoids to adrenal-intact animals diminishes the fever response to LPS, IL-1 and IL-6, probably due to its inhibitory influence on the synthesis of endogenous pyrogens, particularly prostaglandin E, (6)(7)(8). Recent evidence, however, suggests that corticosterone exerts also a permissive influence on the fever response, probably via a central mechanism.…”

“…Recent evidence, however, suggests that corticosterone exerts also a permissive influence on the fever response, probably via a central mechanism. This view stems from the observation that adrenalectomized rats decrease rather than increase body temperature in response to centrally injected IL-1fi and IL-6 ( 8 ) .…”