IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene α (GROα). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROα mRNA and protein. Combination of IL-17 together with TNF-α resulted in an increased stability of GROα mRNA and synergistic release of GROα protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.

The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

Objective To study the metabolism of icodextrin and α–amylase activity following daily exposure to dialysis solutions containing either glucose or icodextrin as osmotic agent in rats. Methods Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL 7.5% icodextrin-based peritoneal dialysis fluid (IPDF; ICO group, n = 12) or 3.86% glucose-based peritoneal dialysis fluid (GLU group, n = 11). A 4-hour dwell study using 30 mL IPDF was performed on day 10 (D1) and day 21 (D2) in both the ICO and the GLU groups. Radiolabeled serum albumin (RISA) was used as a macromolecular volume marker. Dialysate samples were collected at 3, 15, 30, 60, 90, 120, and 240 minutes. Blood samples were drawn before the start and at the end of the dwell. Results During all dwell studies, the dialysate concentrations of total icodextrin decreased due to decrease in high molecular weight (MW) fractions, whereas there was a marked increase in icodextrin low MW metabolites. α–Amylase activity increased in dialysate and decreased in plasma. About 60% of the total icodextrin was absorbed from the peritoneal cavity during the 4-hour dwells. Low MW icodextrin metabolites were present in the dialysate already at 3 minutes, and maltose (G2), maltotriose (G3), maltotetraose (G4), and maltopentaose (G5) increased progressively, reaching maximum concentrations at 60 minutes. Maltohexaose (G6) and maltoheptaose (G7) were also detected already at 3 minutes but did not change significantly during the dwells. During the two 4-hour dwell studies (D1 and D2), the concentrations of total icodextrin and icodextrin metabolites and α–amylase activity in dialysate did not differ between the ICO and GLU groups, during either D1 or D2. No icodextrin metabolites were detected in plasma at the end of the dwells. α–Amylase activity in the dialysate increased six- to eightfold whereas plasma α–amylase activity decreased by 21% – 26% during the two 4-hour dwells in both the ICO and the GLU groups; there were no significant differences between the ICO and the GLU groups during either D1 or D2. α–Amylase activity in the dialysate correlated strongly with the disappearance rate of icodextrin from the peritoneal cavity during the 4-hour dwells, and with the concentrations of G2, G3, G6, and G7 in dialysate. Conclusions The decline in the dialysate concentrations of high MW fractions and the increase in low MW metabolites of icodextrin suggest intraperitoneal α–amylase mediated the metabolism of icodextrin and the transport of predominantly the smaller icodextrin metabolites from dialysate. However, no icodextrin could be detected in plasma, suggesting that it was metabolized and excreted by the kidney in these nonuremic rats. In contrast to uremic peritoneal dialysis patients, chronic exposure to IPDF did not seem to further affect α–amylase activity or icodextrin metabolism. The much higher α–amylase activity in plasma and dialysate in rats than in humans explains the much more rapid metabolism of icodextrin in rats compared with peritoneal dialysis patients.

Heparin may improve peritoneal fluid transport possibly due to better healing and reduced peritoneal inflammation as shown in this novel animal model of chronic peritoneal dialysis with repeated dwell studies.

Objective To assess the in vivo peritoneal inflammatory reaction in rats dialyzed with neutral, bicarbonatelactate-buffered dialysis fluid. Methods Chronic peritoneal dialysis was performed for 4 weeks in Wistar rats with two solutions: (1) 40 mmol/l lactate-buffered fluid, pH 5.2, with a glucose concentration of 2.27 gldl (lac); and, (2) 15 mmolll lactate and 25 mmolll bicarbonate-buffered fluid, pH 7.0 -7.5, with a glucose concentration of 2.27gldl (Bic-lac). After 4 weeks, two peritoneal equilibration tests (PET 1 and PET 2) were performed in all animals with each respective solution. PET 1 was done with test solutions alone, whereas, on a subsequent day, PET 2 was performed with test solutions supplemented with endotoxin [lipopolysaccharide (IPS)] to induce peritonitis. Results During PET 1 no consistent differences were detected in peritoneal permeability between the lac and Bic-lac groups. Total dialysate cell count in the Bic-lac animals was lower than in rats treated with lac fluid: that is, at 8 hours, the respective counts were 1858 ± 524 cellslμl versus 2785 ± 1162 cellslμl (p < 0.01). Dialysate from animals dialyzed with Bic-lac contained more macrophages (at 4 hours: 53.6% ± 35.8% versus 35.8% ± 8.8%, p < 0.001) and fewer neutrophils (at 4 hours: 3.6% ± 1.8% versus 15.4%± 6.1%, p < 0.001) as compared to those dialyzed with the lac solution. Concentration of nitrites in 8-hour dwell dialysate samples from Bic-lac rats was lower than that in the lac group (0.98 ± 0.28 μmollml versus 2.32 ± 0.87 μmollml, p < 0.002), but cytokine levels in the dialysates were comparable. During PET 2, the in -crease in peritoneal permeability resulting from the lPS induced inflammatory response was similar for both test solutions. Dialysate cell count was higher in the lac group versus the Bic-lac group (at 8 hours: 8789 ± 4862 cellslμl versus 3961 ± 581 cellslμl, p < 0.001), contained more neutrophils (at 8 hours: 80.0% ± 11.3% versus 54.8% ± 4.4%, p < 0.001) and fewer macrophages (at 8 hours: 6.8% ± 5.6% versus 21.2% ± 3.3%, p < 0.05). During peritonitis, we found a higher overall dialysate concentration of both tumor necrosis factor (TNFα: +53%, p < 0.05) and of interferon gamma (lFN-y: +303%, p < 0.02), in the Bic-lac group than in the lac group. Conclusions A lower dialysate cell count, higher percentage of macrophages, and lower percentage of neutrophils in dialysate suggest that Bic-lac fluid induces a diminished nonspecific inflammatory response of the peritoneal cavity during dialysis. However, after in vivo stimulation, peritoneal cells from animals dialyzed with Bic-lac solution possess an augmented ability to produce inflammatory cytokines.