Hyaluronan modifies inflammatory response and peritoneal permeability during peritonitis in rats

The effect of high-molecular-weight hyaluronan (HA) on peritoneal and syste mic inflammation and peritoneal permeability to water and solutes was studi ed during endotoxin-induced peritonitis in rats. Acute peritonitis was indu ced by adding lipopolysaccharide (LPS) to the dialysis fluid (Dianeal 3.86; Baxter Healthcare, Ireland, Castlebar). HA was added to the dialysis solut ion in a concentration of 10 mg/dL. During 4- and 8-hour dwells of the dial ysis fluid, we studied the intensity of peritoneal (dialysate) and systemic (blood) inflammation (dialysate cell count and differential, cytokine and HA levels), as well as the transperitoneal transport of solutes and water. In rats, the addition of LPS to the dialysis fluid induced changes in infla mmatory reaction and transperitoneal transport similar to those seen in con tinuous ambulatory peritoneal dialysis patients with peritonitis. During pe ritonitis, the addition of HA to the dialysis fluid reduced the loss of ult rafiltration, which resulted in a greater peritoneal creatinine clearance d uring the 8 hours of dwell (29.9 +/- 6.7 mL/8 h in the HA-LPS group versus 19.7 +/- 7.8 mL/8 h in the LPS group; P < 0.05). Dialysate interferon-<gamm a> (INF-gamma) levels during peritonitis were greater in HA-treated animals (536.8 +/- 296.6 pg/mL in the HA-LPS group versus 169.8 +/- 137.8 pg/mL in the LPS group; P < 0.05). Dialysate elastase activity increased during per itonitis (44.4 +/- 9.3 versus 14.2 +/- 4.1 U/mL in peritonitis-free rats); during peritonitis, the increase in dialysate elastase activity was less pr onounced in the rats that had HA in the dialysate (27.3 +/- 4.1 U/mL versus the LPS group; P < 0.01). We conclude that HA added to the dialysis fluid reduces loss of ultrafiltration during peritonitis in rats. In the presence of HA dialysate, INF-gamma levels during peritonitis increased, whereas el astase activity decreased; these changes might improve the peritoneal immun e reaction during peritonitis and at the same time prevent peritoneal membr ane injury. (C) 2001 by the National Kidney Foundation, Inc.