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

Abstract

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.

The aldosterone receptor antagonist spironolactone prevents peritoneal inflammation and fibrosis

“…These substances are known to damage the structural integrity of the peritoneum by targeting peritoneal mesothelial cells, eventually resulting in fibrosis and loss of peritoneal function. [17][18][19][20][21] A key role for macrophages in fibrosis has been observed in diverse organ settings. In PD patients, compared with uninfected patients, macrophages display an upregulation ex vivo.…”

Monocyte-Related Determinants of Inflammation in Patients on Peritoneal Dialysis

“…Different methodological approaches have been used to address the question whether uremia and dialysis influence MCP-1 concentrations [23][24][25]. Sach et al [24] found increased concentrations of MCP-1 in dialysate effluents of continuous ambulatory PD patients with peritonitis, and Akahoshi et al [23] reported increased serum levels of MCP-1 in hemodialysis patients, while Pertosa et al [25], by use of an in vitro method, reported a significantly lower spontaneous production of MCP-1 from mononuclear cells of uremic patients and patients on dialysis. Thus, methodological considerations have to be taken into account when interpreting MCP-1 data in patients with renal insufficiency and in those on dialysis.…”

Hyaluronan fragments induce the synthesis of MCP-1 and IL-8 in cultured human peritoneal mesothelial cells

“…MCP-1 is a C-C chemokine and has been shown to be a very effective monocyte chemoattractant and activator (Schlondorff et al 1997;Tekstra et al 1996). In recent studies, high levels of the chemokines MCP-1 and IL-8 were detected in the effluent of PD patients suffering from bacterial peritonitis (Tekstra et al 1996;Sach et al 1997). However, even after recovery from the infection, a continuous production of these chemokines was observed (Zemel et al 1994), in particular with high MCP-1 levels in steady-state peritoneal dialysates (Tekstra et al 1996).…”