Effect of indomethacin on peritoneal protein loss in a rabbit model of peritonitis

Background. Although various inflammatory mediators have been previously sh own to be released into the peritoneal cavity during peritonitis in periton eal dialysis patients, those that are involved in governing changes in peri toneal permeability to small solutes and protein remain incompletely define d. Methods. We determined the importance of prostanoid production in the enhan ced protein loss observed during acute peritonitis by inhibition experiment s using indomethacin, an inhibitor of cyclooxygenase activity. The associat ion between changes in peritoneal permeability and the generation of inflam matory mediators after adding Escherichia coli to peritoneal dialysate was first examined in series 1 experiments. Series 2 experiments then determine d the effect of intraperitoneal administration of indomethacin (75 mug/mL) on changes in peritoneal permeability after adding E. coli to peritoneal di alysate. All experiments were performed in male New Zealand White rabbits ( 2.6 to 3.4 kg body weight) using an eight-hour dwell of dialysate containin g 2.5% glucose. Peritoneal permeability to creatinine and protein was asses sed by time-dependent changes in the dialysate to plasma concentration rati os of these solutes. Results. Series 1 experiments showed enhanced leukocyte migration into the peritoneal cavity and increased peritoneal permeability to protein during b acterial challenge that was accompanied by an increase in the dialysate con centrations of prostaglandin E-2 (PGE(2)), 6-keto-PGF(1 alpha), and interle ukin-8, but not nitrate + nitrite (a measure of local nitric oxide producti on). Inhibition of prostanoid production by intraperitoneal administration of indomethacin in series 2 experiments resulted in lower dialysate concent rations of PGE(2) and 6-keto-PGF(1 alpha) and in lower peritoneal permeabil ity to protein, both to control levels. No effect of indomethacin on transp eritoneal migration of leukocytes or the generation of interleukin-8 was ob served. Conclusions. Enhanced production of prostanoids likely plays an important r ole in governing the increase in peritoneal permeability to protein during acute, bacterial peritonitis in the rabbit.