Effect of monophosphoryl lipid A on the in vitro function of peritoneal leukocytes from uremic patients on continuous ambulatory peritoneal dialysis

Abstract

We analyzed the effects of monophosphoryl lipid A (MPL), a relatively nontoxic immunostimulant derived from bacterial endotoxin, on the depressed in vitro immune function of leukoxytes derived from six patients undergoing continuous ambulatory peritoneal dialysis and who had histories of recurrent bacterial peritonitis. MPL was also tested for its capacity to stimulate the proliferation of peritoneal fibroblasts, as determined by [3H]thymidine incorporation. In vitro incubation of peritoneal lymphocytes and macrophages (PMΦ) with increasing amounts of MPL, up to 5 μg/ml, resulted in a dose-dependent enhancement of gamma interferon and interleukin-2 production by peritoneal lymphocytes and interleukin-1 release by PMΦ. In vitro incubation of PMΦ with MPL also resulted in an increase of PMΦ bacterial killing and membrane Fc receptor number, although no change in peritoneal fibroblast proliferation was seen with any of the MPL concentrations tested. These results suggest that the peritoneal leukocyte dysfunction observed in patients undergoing continuous ambulatory peritoneal dialysis and who have high rates of peritonitis may be alleviated, to some degree, by MPL, without directly inducing a potentially deleterious fibrotic lesion.