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 macroph ages (PMO) may influence the cytokine network controlling peritoneal i nflammation and in the long-term the function of the peritoneum as a d ialysis membrane. In the present study, an evaluation of the long-term effects of peritoneal dialysis on the release of cytokines and prosta glandins, 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 facto r alpha (TNF alpha) and interleukin 6 (IL-6) by PMO, after 4 or 24 hou rs in culture, increased significantly with time on CAPD, while there was a small but significant decrease in release of prostaglandin E(2) (PGE(2)). Production of TNF alpha and IL-6 was enhanced following incu bation of the cells with lipopolysaccharide (LPS), but the effect of L PS was proportionally greater on blood monocytes than on PMO. There wa s a significant increase in thr concentrations of PGE, and 6-keto-pros taglandin F-1 alpha in overnight dwell peritoneal dialysis effluent wi th time on CAPD. The levels of TNF alpha and IL-B in uninfected PDE we re below the detection limit of the immunoassay over the whole time pe riod studied. Expression of CD15, which correlates with immaturity, by PMO and blood monocytes increased with time on CAPD, while expression of CD11c, a marker of maturation, decreased on blood monocytes, but d id not change significantly on PMO. There was also a slight increase i n expression of transferrin receptor in both PMO and monocytes, but th is did not reach statistical significance. These findings suggest that peritoneal macrophages and blood monocytes isolated from CAPD patient s over a one year period become increasingly immature with time, and t his is accompanied by a significant modulation of their ability to sec rete 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.