Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal mesothelial cell interleukin-6 and prostaglandin synthesis

Witowski, Janusz, Topley, Nicholas, Jörres, Achim, Liberek, Tomasz, Coles, Gerald A. and Williams, John D. 1995. Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal mesothelial cell interleukin-6 and prostaglandin synthesis. Kidney International 47 (1) , pp. 282-293. 10.1038/ki.1995.36

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Abstract

Effect of lactate-buffered peritoneal dialysis fluids on human mesothelial cell interleukin-6 and prostaglandin synthesis. The present study focused on the evaluation of constitutive and cytokine-stimulated human peritoneal mesothelial cell (HPMC) IL-6 and 6-keto-PGF1alpha, release following pre-exposure to peritoneal dialysis fluid (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-1beta stimulated IL-6 and 6-keto-PGF1alpha synthesis. After 15 minutes of exposure to PDF constitutive and IL-1beta stimulated IL-6 release were reduced by 32.0 plusminus 9.7% and 76.0 plusminus 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-1beta stimulated IL-6 and cyclooxygenase (Cox-1 and Cox-2) transcripts. In order to mimic the dialysis cycle in vivo, an in vitro dialysis system was established. HPMC were exposed first to control medium, PDF pH 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 subsequently allowed to recover in control medium for 12 hours in the presence or absence of IL-1beta or TNF-alpha (both at 1000 pg/ml). There was no evidence of significant cell toxicity as assessed by LDH release during either the 'in vitro dialysis" or 'recovery" phases. Under these conditions short term exposure to PDF pH 5.2 followed by 'in vitro dialysis" resulted in significant inhibition of cytokine stimulated IL-6 (69.6 plusminus 18.2 vs. 96.7 plusminus 27.9 pg/microg, N = 13; P < 0.020 for IL-1beta) and 6-keto-PGF1alpha (197.5 plusminus 89.2 vs. 289.6 plusminus 114.5 pg/microg, N = 13; P < 0.020 for IL-1beta) and 6-keto-PGF1alpha (197.5 plusminus 89.2 vs. 289.6 plusminus 114.5 pg/microg, N = 13; P < 0.003) release when 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 prostaglandin release, an effect which appears to be related to its initial pH. Repeated exposure to nonphysiological PDF might impair mesothelial cell function and thus modulate intraperitoneal inflammatory processes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > Q Science (General) R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Publisher:	Nature Publishing Group
ISSN:	0085-2538
Last Modified:	30 Jun 2017 03:03
URI:	https://orca.cardiff.ac.uk/id/eprint/46381

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