The effect of fresh peritoneal dialysis (PD) solution and effluent on the generation of eicosanoids and cytokines by human peritoneal macrophages (PMO) was studied in vitro. PMO, isolated by density gradient separation from patients undergoing intermittent peritoneal dialysis (IPD), were incubated for 2 h with PD effluent after dwell periods of 5 to 240 min or fresh PD solution. Supplemented RPMI-1640 medium served as control. PMO were stimulated by calcium ionophore A23187 (10 M). PD solution significantly inhibited the release of prostanoids (PGE2, TXB2, 6-k-PGF1), leukotrienes (LTB4, LTC4), and cytokines (11-6, TNF) from PMO by 60 to 96% (p < 0.05). Addition of A23187 increased the generation of TXB2, LTB4, and LTC4 in PD solution adjusted to pH 7.4 to 2.7 up to 28.6 times the basal level, but was ineffective in PD fluid at pH 5.2. Incubation of PMO with PD effluent of varying dwell times resulted in a rise of all assayed mediators (p < 0.05). The release of IL-6 increased continuously from 80 +/- 10 pg/10(6) PMO (0 min dwell time) to 440 +/- 104 pg/10(6) PMO (4 h dwell time, mean +/- S.E.M.). TNF generation rose from 6.0 +/- 0.1 pg/10(6) PMO (0 min dwell time) to 162 +/- 54 pg/10(6) PMO after 5 min dwell time and remained constant with effluents of longer dwell times (15 to 240 min). Exposure of PMO to PD effluents after 240 min dwell time tended to decrease the median levels of PGE2, TXB2, and 6-k-PGF1.(ABSTRACT TRUNCATED AT 250 WORDS)