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An important event in intraperitoneal inflammation is the influx of leukocytes into the peritoneal cavity. Chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) play a major role in the recruitment of immune cells to the site of inflammation. We determined the concentrations of two members of the chemokine family, IL-8 and MCP-1, in the dialysate effluents of 18 continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis and of 18 non-infected CAPD patients by specific enzyme-linked immunosorbent assays (ELISA). Isolated peritoneal macrophages (PMs) from CAPD peritonitis patients were cultured and IL-8 and MCP-1 production was determined on protein (ELISA) and mRNA level (Northern blot) at designated timepoints over a 72-h culture period. PMs from non-infected patients served as controls. Much higher concentrations of IL-8 and MCP-1 were found in dialysate effluents of peritonitis patients than in effluents of non-infected patients: IL-8 2.39 +/- 1.15 vs 0.05 +/- 0.01 ng/ml and MCP-1 22.5 +/- 6.27 vs 0.42 +/- 0.07 ng/ml. IL-8 and MCP-1 release by cultured PMs from peritonitis patients and non-infected patients revealed significant differences: IL-8 40.3 +/- 2.2 ng/ml after 3 h and 194.2 +/- 34.9 ng/ml after 12 h compared to 21.02 +/- 6.15 ng/ml after 3 h and 89.64 +/- 30.28 ng/ml after 12 h, respectively; MCP-1 3.3 +/- 0.9 ng/ml after 3 h and 25.7 +/- 7.4 ng/ml after 12 h compared to 1.1 +/- 0.2 ng/ml and 1.8 +/- 0.2 ng/ml, respectively. Interestingly, the ratio of IL-8 to MCP-1 concentrations in the dialysate effluents (1:9.4) is reversed in the supernatants of cultured PMs. In the effluents and in the culture supernatants of PMs from CAPD peritonitis patients high amounts of IL-8 and MCP-1 are detectable, suggesting that PMs are an important source for these chemokines during peritonitis. Because of the inverse ratio of IL-8 and MCP-1 in the effluents and culture supernatants it can be assumed that PMs are responsible for the MCP-1 concentration to a lesser extent than for the IL-8 concentration in the effluents.

Inverse MCP-1/IL-8 ration in effluents of CAPD patients with peritonitis and in isolated cultured human peritoneal macrophages