RESTORATION OF POSTBURN IMPAIRED LYMPHOCYTE RESPONSIVENESS BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS IS INDEPENDENT OF PROSTAGLANDIN E(2) INHIBITION

Prostaglandin E(2) (PGE(2)) has been implicated in postburn immunosupp ression, which is responsible for septic complications. In the present work, seven nonsteroidal anti-inflammatory drugs (NSAIDs), differing by their capacity to inhibit the cyclooxygenase pathway, were compared for their ability to restore T lymphocyte proliferative responses eva luated 4 days after thermal injury in rats. Salicylic acid, 5-aminosal icylic acid, and niflumic acid, given daily, fully restored spleen cel l responses to concanavalin A (Con A) and phytohemagglutinin. These dr ugs were active only at doses that were below the anti-inflammatory do ses and did not modify normal spleen cell responses. In these conditio ns, indomethacin slightly restored lymphocyte reactivity, whereas acet ylsalicylic acid, ketoprofene, and piroxicam were ineffective. PGE(2) production by Con A-stimulated spleen cells from untreated burned rats and after treatment with niflumic acid or 5-aminosalicylic acid did n ot correlate with the intensity of the proliferative response. Indomet hacin, 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. PGE(2) production was strongly depressed by indomethac in and niflumic acid and not modified by 5-aminosalicylic acid. The pr oliferative response of normal spleen cells was depressed in a concent ration-dependent manner by niflumic acid and slightly inhibited at the highest concentrations of indomethacin. In contrast, indomethacin con centration dependently restored the burn-impaired proliferative respon se, whereas niflumic acid further depressed it and 5-aminosalicylic ac id 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 PGE(2) producti on.