Restoration of postburn impaired lymphocyte responsiveness by nonsteroidal anti-inflammatory drugs is independent of prostaglandin E2 inhibition.
Prostaglandin E2 (PGE2) has been implicated in postburn immunosuppression, which is responsible for septic complications. In the present work, seven non-steroidal anti-inflammatory drugs (NSAIDs), differing by their capacity to inhibit the cyclooxygenase pathway, were compared for their ability to restore T lymphocyte proliferative responses evaluated 4 days after thermal injury in rats. Salicylic acid, 5-aminosalicylic acid, and niflumic acid, given daily, fully restored spleen cell responses to concanavalin A (Con A) and phytohemagglutinin. These drugs were active only at doses that were below the anti-inflammatory doses and did not modify normal spleen cell responses. In these conditions, indomethacin slightly restored lymphocyte reactivity, whereas acetylsalicylic acid, ketoprofen, and piroxicam were ineffective. PGE2 production by Con A-stimulated spleen cells from untreated burned rats and after treatment with niflumic acid or 5-aminosalicylic acid did not correlate with the intensity of the proliferative response. Indomethacin, niflumic acid, and 5-aminosalicylic acid were added in vitro to spleen cells from normal and burned rats, at concentrations from 10(-7) to 10(-4) M. PGE2 production was strongly depressed by indomethacin and niflumic acid and not modified by 5-aminosalicylic acid. The proliferative response of normal spleen cells was depressed in a concentration-dependent manner by niflumic acid and slightly inhibited at the highest concentrations of indomethacin. In contrast, indomethacin concentration dependently restored the burn-impaired proliferative response, whereas niflumic acid further depressed it and 5-aminosalicylic acid had no effect. These results demonstrate that only some NSAIDs are able to restore T lymphocyte reactivity impaired after thermal injury and that this property is not related to inhibition of PGE2 production.
Mathieu
J
J
Unité de Radiobiochimie, Centre de Recherche du Service de Santé des Armées (CRSSA), Université Paris V, France.
Masson
I
I
Chancerelle
Y
Y
Chanaud
B
B
Strazlko
S
S
De Sousa
M
M
Kergonou
J F
JF
Giroud
J P
JP
Florentin
I
I
D000284:Administration, Oral; D000594:Amino Acid Oxidoreductases / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002056:Burns / Q000276:immunology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D010894:Piroxicam / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; D010894:Piroxicam; D009544:Niflumic Acid; D007660:Ketoprofen; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015232:Dinoprostone; D007213:Indomethacin