The effect of indomethacin on the cytokine cascade and body temperature following burn injury in rats

This study investigates the hypothesis that indomethacin's ability to preve nt "fever" following burn injury in rats is mediated via decreased plasma c oncentrations of IL-6, the putative mediator of increased body temperature. Sprague-Dawley rats had radio transmitters and osmotic pumps containing in domethacin placed in the peritoneal cavity. Seven days later full thickness scald burns to 50% of the body surface area were produced. Following burn injuries, daily blood samples were obtained from a carotid catheter for ass ay of lipopolysaccharide (LPS), interleukin-1 alpha (IL-1 alpha), IL-1 beta , tumor necrosis factor-alpha (TNF-alpha) and IL-6. In addition, body tempe rature (TB) and activity index were obtained every five minutes by telemetr y. There were four experimental groups: burn+indomethacin (B-In); burn+poly ethylene glycol (Peg) (B-Peg); control+ indomethacin (C-In); and control+Pe g (C-Peg). Burned animals demonstrated a significant two-fold increase in p lasma IL-1 alpha levels (p=0.004) and a seven-fold increment in IL-6 (p = 0 .0001) through the 7th PBD, and indomethacin administration had no signific ant effect upon the cytokine plasma levels. There were no significant incre ases in IL-1 beta, TNF-alpha or LPS in any group. Indomethacin eliminated t he chronic increase in T-B following burn injury, and this effect was not p roduced by changes in plasma levels of the endogenous pyrogens IL-1 alpha a nd IL-6. (C) 1999 Elsevier Science Ltd and ISBI. All rights reserved.