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 prevent "fever" following burn injury in rats is mediated via decreased plasma concentrations of IL-6, the putative mediator of increased body temperature. Sprague-Dawley rats had radio transmitters and osmotic pumps containing indomethacin 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 assay of lipopolysaccharide (LPS), interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6. In addition, body temperature (T(B)) and activity index were obtained every five minutes by telemetry. There were four experimental groups: burn + indomethacin (B-In); burn + polyethylene glycol (Peg) (B-Peg); control + indomethacin (C-In); and control + Peg (C-Peg). Burned animals demonstrated a significant two-fold increase in plasma IL-1alpha levels (p=0.004) and a seven-fold increment in IL-6 (p=0.0001) through the 7th PBD, and indomethacin administration had no significant effect upon the cytokine plasma levels. There were no significant increases in IL-1beta, TNF-alpha or LPS in any group. Indomethacin eliminated the chronic increase in T(B) following burn injury, and this effect was not produced by changes in plasma levels of the endogenous pyrogens IL-1alpha and IL-6.
Caldwell
F T
FT
University of Arkansas, Department of Surgery, Little Rock 72205, USA. wallacebonnyb@exchange.uams.edu
Graves
D B
DB
Wallace
B H
BH
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001830:Body Surface Area; D001831:Body Temperature / Q000187:drug effects*; D002056:Burns / Q000473:pathology / Q000503:physiopathology*; D002406:Catheterization, Peripheral; D016207:Cytokines / Q000187:drug effects*; D004195:Disease Models, Animal; D006400:Hematocrit; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D015918:Infusion Pumps, Implantable; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000502:physiology; D010529:Peritoneal Cavity / Q000601:surgery; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011749:Pyrogens / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000627:therapeutic use; D013686:Telemetry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011749:Pyrogens; D013501:Surface-Active Agents; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D007213:Indomethacin