Longitudinal evaluation of peritoneal macrophage function and activation during CAPD: maturity, cytokine synthesis and arachidonic acid metabolism.
The release of cytokines and prostaglandins (PG) by peritoneal macrophages (PM luminal diameter of) may influence the cytokine network controlling peritoneal inflammation and in the long-term the function of the peritoneum as a dialysis membrane. In the present study, an evaluation of the long-term effects of peritoneal dialysis on the release of cytokines and prostaglandins, and the expression of surface markers of cellular maturation on blood and mononuclear cells has been performed in patients during their first year on CAPD. Spontaneous release of tumour necrosis factor alpha (TNF alpha) and interleukins 6 (IL-6) by PM luminal diameter of, after 4 or 24 hours in culture, increased significantly with time on CAPD, while there was a small but significant decrease in release of prostaglandin E2 (PGE2). Production of TNF alpha and IL-6 was enhanced following incubation of the cells with lipopolysaccharide (LPS), but the effect of LPS was proportionally greater on blood monocytes than on PM luminal diameter of. There was a significant increase in the concentrations of PGE2 and 6-keto-prostaglandin F1 alpha in overnight dwell peritoneal dialysis effluent with time on CAPD. The levels of TNF alpha and IL-6 in uninfected PDE were below the detection limit of the immunoassay over the whole time period studied. Expression of CD15, which correlates with immaturity, by PM luminal diameter of and blood monocytes increased with time on CAPD, while expression of CD11c, a marker of maturation, decreased on blood monocytes, but did not change significantly on PM luminal diameter of. There was also a slight increase in expression of transferrin receptor in both PM luminal diameter of and monocytes, but this did not reach statistical significance. These findings suggest that peritoneal macrophages and blood monocytes isolated from CAPD patients over a one year period become increasingly immature with time, and this is accompanied by a significant modulation of their ability to secrete inflammatory cytokines. Dysregulation of macrophage function may have important consequences with respect to inflammatory processes and the long-term function of the peritoneal membrane in CAPD patients.
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