Induction of prostaglandin synthesis-dependent suppressor cells with endotoxin: occurrence in patients with thermal injuries

Abstract

The induction of lymphocyte suppressor activity with bacterial endotoxin is well documented. While most of the evidence has been obtained using animal models and has required large doses of endotoxin, we have demonstrated that additions of as little as 1.0 ng of chromatographically purified endotoxin [from Escherichia coli 055:B5, E. coli 0111:B4, Pseudomonas aeruginosa (Fisher-Devlin immunotype 1), Serratia marcescens, or Salmonella minnesota] to human mixed lymphocyte or to mitogen-stimulated cultures produced statistically significant suppression. In each case, endotoxin was most suppressive when present in the culture system prior to the introduction of the alloantigen or mitogen. Suppressive effects were dependent upon the participation of peripheral blood monocytes and could be blocked by the addition of the prostaglandin synthetase inhibitor indomethacin or meclofenamate sodium. Prostaglandin production by monocytes appeared to induce a population of "short-lived" suppressor cells, identified by the immediate and delayed addition of lymphocyte cocultures to endotoxin-preincubated cells. The suppressive behavior of endotoxin-primed lymphocytes was identical to the behavior of burn patient serum-primed lymphocytes or to lymphocyte populations derived from a subpopulation of burn patients whose serum was Limulus positive. We, therefore, feel that endotoxin plays a significant immunologic role in these patients.