EFFECTS OF INTRAPERITONEAL CYCLOOXYGENASE INHIBITION ON INFLAMMATORY MEDIATORS IN DIALYSATE AND PERITONEAL MEMBRANE-CHARACTERISTICS DURING PERITONITIS IN CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS

Peritonitis complicating continuous ambulatory peritoneal dialysis (CA PD) can be used as an in vivo model to study the contribution of media tors in dialysate to the regulation of peritoneal permeability. Previo usly we reported that changes in the peritoneal appearance rates of th e cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) were related to alterations in the effective peritoneal surface area. Changes in the intrinsic peritoneal permeability were mainly re lated to those in the peritoneal appearance rate of the prostanoid pro staglandin E(2) (PGE(2)) and partly also to that of IL-6. In this inte rvention study the role of these mediators was further analyzed. Eleve n peritonitis episodes were followed on 8 consecutive days from the st art of the infection and once oner recovery. Indomethacin was given in traperitoneally during the first 3 days. beta(3)-Microglobulin clearan ce was used as indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized functionally by t he restriction coefficient. The 15 peritonitis episodes studied previo usly served as the control group. This study supports the formerly obt ained relationships in two ways. First, significant reductions were ob served for peritoneal PGE(2), 6-keto-PGF(1 alpha), and TxB(2) during c yclooxygenase inhibition to 6%, 0.6%, and 9% of the values on day 1, w hereas simultaneously the intrinsic permeability was less increased. T his indomethacin effect on intrinsic permeability was not entirely sig nificant, probably because of the additional role of IL-6, which was n ot influenced by indomethacin. Also, the appearance rate of TNF alpha in the effluent was not affected by cyclooxygenase inhibition. Accordi ngly, the changes in the effective surface area were similar to those in the control group. Second, in 8 of the 11 cases, new rises both in peritoneal PGE, and in intrinsic permeability occurred after discontin uation of indomethacin. Rebounds were not seen for TNF alpha or IL-6, and, consistently, not for the effective surface area. In conclusion, local cyclooxygenase inhibition results in a less-increased intrinsic permeability during peritonitis but has no effect on the effective sur face area. These data support our previous finding that IL-6 and TNF a lpha contribute to alterations in surface area, whereas PGE(2) is more involved in intrinsic peritoneal permeability changes,