Cyclooxygenase 2-mediated suppression of macrophage interleukin-12 production after thermal injury.
Macrophage (Mphi) prostaglandin (PG)E(2) production has been implicated in immunosuppression and increased susceptibility to sepsis after thermal injury. Deficient interleukin (IL)-12 production has also been implicated in these postburn complications. The present study examined the relationship between Mphi cyclooxygenase (COX)-2 activity and IL-12 production after thermal injury. C57BL/6 female mice were subjected to a 25% total body surface area full-thickness burn. Mphi were isolated 7 days later, or the mice were subjected to sepsis by cecal ligation and puncture (CLP). IL-12 production by Mphi from injured mice was suppressed by >50%, whereas COX-2 expression and PGE(2) production were increased twofold. The COX-2 inhibitor NS-398 suppressed PGE(2) production and normalized IL-12 production in the injury group, whereas it had no effect on IL-10 production. Injured mice subjected to CLP had lower IL-12 plasma levels compared with sham-treated mice subjected to CLP. NS-398 treatment prevented the suppression in plasma IL-12 levels in the injury group. Thus elevated Mphi COX-2 activity, independent of IL-10, suppresses Mphi IL-12 production after thermal injury and may play an important role in the observed immunosuppression under such conditions.
Schwacha
Martin G
MG
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, 35294, USA. Martin.Schwacha@ccc.uab.edu
Chung
Chun-Shiang
CS
Ayala
Alfred
A
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D001424:Bacterial Infections / Q000097:blood / Q000150:complications; D002056:Burns / Q000150:complications / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016753:Interleukin-10; D018664:Interleukin-12; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases