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

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.

Isolation immunosuppressive serum components following thermal injury.

There has been increasing recognition in recent literature that immunoregulatory factors can often be detected in the serum of patients with thermal and traumatic injuries. We, too, have shown that a significant number of patients with severe thermal injuries are profoundly immunosuppressed. This immunosuppression was mediated by substances which circulate in the serum which could be easily detected using in vitro lymphocyte assays. The suppressive material was not present in normal serum, and exerted its effects through the activity of a specific (suppressor) subpopulation of lymphocytes. In this study, we have analyzed serum samples obtained from burn patients by plasmapheresis for suppressive activity, then fractionated each using Sephadex G-200. Individual fractions were tested for suppressive activity in mixed lymphocyte cultures, and approximate molecular weights established for suppressive peaks by means of chromatography calibration standards. Evidence linking suppressive activity of the sera to the presence of endotoxin, prostaglandin E, interferon, and "cutaneous burn toxin' is discussed.