Effect of indomethacin and Impact liquid diet administration on inflammatory mediator production by murine splenocytes after burn injury.
Production of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) by various cells is increased after injury, and these mediators are implicated in the downregulation of immune responses. We attempted to modulate the production of immune suppressive mediators by inhibiting prostaglandin production in a murine model that had a burn covering 25% of the total body surface area. Two treatments were performed. One was the intraperitoneal administration of indomethacin after burn injury at 2 mg/kg day for 10 days. The control group received saline solution injections. The other treatment was the ad libitum administration of a commercial diet after burn injury for 10 days. This diet contained mixed fats, including omega-3 and omega-6 fatty acids. The control group received standard mouse food. On days 1, 5, and 10 after burn injury, spleens were removed aseptically, and splenocyte cultures were established and stimulated with phytohemagglutinin. TNF-alpha and PGE2 concentrations were determined in culture supernatants at 48 hours with the use of commercial enzyme-linked immunosorbent assay kits. Splenocytes from burned animals produced elevated levels of both mediators in culture supernatants, reaching significant levels of TNF-alpha on day 10 after burn injury and of PGE2 on days 5 and 10 after burn injury. Neither the administration of indomethacin for 10 days nor the administration of the commercial diet for 10 days decreased production of these mediators in culture. However, cells in culture may escape the in vivo regulating effects of biologic modifying agents.
Zapata-Sirvent
R L
RL
Department of Surgery, University of California, San Diego 92103.
Hansbrough
J F
JF
D000818:Animals; D002056:Burns / Q000378:metabolism*; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004041:Dietary Fats; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007213:Indomethacin