EFFECT OF LACTATE-BUFFERED PERITONEAL-DIALYSIS FLUIDS ON HUMAN PERITONEAL MESOTHELIAL CELL INTERLEUKIN-6 AND PROSTAGLANDIN SYNTHESIS

The present study focused on the evaluation of constitutive and cytoki ne-stimulated human peritoneal mesothelial cell (HPMC) IL-6 and 6-keto -PGF(1 alpha) release following pre-exposure to peritoneal dialysis fl uid (PDF). Exposure of HPMC to PDF pH 5.2 resulted in a time-dependent increase in cell cytotoxicity [as assessed by lactate dehydrogenase ( LDH) release] and concomitant inhibition of constitutive and IL-1 beta stimulated IL-6 and 6-keto-PGF(1 alpha) synthesis. After 15 minutes o f exposure to PDF constitutive and IL-1 beta stimulated IL-6 release w ere reduced by 32.0 +/- 9.7% and 76.0 +/- 7.4% (N = 6, P < 0.046 and P < 0.027, respectively). PCR amplification of reverse transcribed mRNA from HPMC pre-exposed to PDF pH 5.2 demonstrated suppression of IL-1 beta stimulated IL-6 and cyclooxygenase (Cox-1 and Cox-2) transcripts. In order to mimic the dialysis cycle in vivo, an in vitro dialysis sy stem was established. HPMC were exposed first to control medium, PDF p H 5.2 or PDF 7.3 for 15 minutes and then sequentially to pooled spent peritoneal dialysis effluent for up to four hours. The cells were subs equently allowed to recover in control medium for 12 hours in the pres ence or absence of IL-1 beta or TNF-alpha (both at 1000 pg/ml). There was no evidence of significant cell toxicity as assessed by LDH releas e during either the 'in vitro dialysis' or 'recovery' phases. Under th ese conditions short term exposure to PDF pH 5.2 followed by 'in vitro dialysis' resulted in significant inhibition of cytokine stimulated I L-6 (69.6 +/- 18.2 vs. 96.7 +/- 27.9 pg/mu g, N = 13; P < 0.020 for IL -1 beta) and 6-keto-PGF(1 alpha) (197.5 +/- 89.2 vs. 289.6 +/- 114.5 p g/mu g, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF(1 alpha) (197. 5 +/- 89.2 vs. 289.6 +/- 114.5 pg/mu g, N = 13; P < 0.003) release whe n compared to cells incubated in control medium. Adjustment of the pH of PDF to 7.3 reversed its inhibitory effects. We conclude that short- term exposure to PDF pH 5.2 significantly inhibits HPMC cytokine and p rostaglandin release, an effect which appears to be related to its ini tial pH. Repeated exposure to nonphysiological PDF might impair mesoth elial cell function and thus modulate intraperitoneal inflammatory pro cesses.