Inhibition of Cytokine Synthesis by Peritoneal Dialysate Persists throughout the CAPD Cycle

Abstract

The current study focused on the effect of continuous ambulatory peritoneal dialysis (CAPD) dialysate obtained following different intraperitoneal dwell periods on the release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFa) from mononuclear leukocytes (PBMC). Aliquots of 5 X 10⁶/ml healthy peripheral PBMC were exposed to fresh or spent CAPD dialysate (10-240 min of intra-peritoneal dwell) and stimulated with Escherichia coli endotoxin (10 jxg/ml, 2 h). IL-6 and TNFa in cell supernatants were determined by specific enzyme immunoassays. Control PBMC in physiological buffer released 361 ± 70 pg/ml IL-6 and 717 ± 147 pg/ml TNFa (mean ± SEM, n = 8), whereas exposure to fresh dialysis fluids severely suppressed cytokine release from PBMC ( < 30 pg/ml IL-6 and < 15 pg/ml TNFa). A significant inhibition of IL-6 and TNFa release was also observed in PBMC exposed to spent dialysate. The inhibitory capacity of the spent fluids was pronounced with increasing intra-peritoneal dwell time (10 min: 183 ± 45 pg/ml IL-6 and 538 ± 109 pg/ml TNFa; 240 min: 26 ± 5 pg/ml IL-6 and 105 ± 30 pg/ml TNFa; mean ± SEM, n = 16). These data indicate that the impairment of cell responsiveness following exposure of PBMC to peritoneal dialysate is not restricted to the unused fluids, but is also observed following intra-peritoneal equilibration. Moreover, our findings suggest the presence of cytokine inhibitory factors in the peritoneal dialysate of CAPD patients which appear to accumulate in the peritoneal effluent during the CAPD cycle.

Automated Peritoneal Dialysis Symposium: Host Defenses in APD

“…The capability of PMOs to produce cytokines in response to LPS stimulation was significantly decreased by APD. This effect has also been shown in PMOs from CAPD patients under PD, which were inhibited in re; easing cytokines after a stimulus such as TNF‐α (25,26,41,42), IL‐1β(41–43), or IL‐6 (26,27). With every exchange a milieu toxic to phagocytes is created by the high osmolality, low pH of fresh glucose‐based dialysis solution (23,44), and lactate content of the solution (45,46).…”

“…After 7 minutes dwell in the peritoneal cavity the dialysis solution's pH adjusts from 5.5 to 6.8 (47) and after 30 minutes it reaches 7.3 (44), which is then nontoxic for leukocytes. The changes in osmolality, however, are less rapid and may remain at inhibitory levels for longer periods of time, as was demonstrated in vitro and ex vivo (22,26,44) As was shown in vitro, spent dialysate obtained after a 4‐hour dwell from CAPD patients also suppressed cytokine release in PMO (26).…”

“…This was attributed to the high osmolality and low pH of the PD dialysate (22,23), and to the lactate buffer of the dialysate (24). Furthermore, it was shown that the PMO capacity to release cytokines was decreased as a result of the dialysate exposure (25–27). These host defense mechanisms recover with longer dialysate dwell times (20) and may possibly further benefit from an intermittent technique of PD (intervals without rapid exchanges of dialysate) (28).…”

Systemic liberation of interleukin- 1β and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation

“…Patients in both the FK 506 and CyA groups were treated according to an immunosuppressive regimen described elsewhere [22]. This included methylprednisolone (MP), azathioprine, and antithymocyte globulin (ATG; Fresenius, Bad Homburg, Germany).…”

“…Enzyme immunoassays were performed in microtiter strips (Nunc, Roskilde, Denmark) as previously described for IL-6 and TNF-a [22]. The following antibodies were used: for the IL-lra assay, poly- clonal anti-IL-lra antibody (R + D Systems, Bad Nauheim, Germany); for the IL-lp assay, monoclonal anti-IL-lp antibody (Biogenesis, Bournemouth, UK); for the IL-6 assay, mouse monoclonal anti-human IL-6 antibody (Serva, Heidelberg, Germany); and for the TNF-a assay, mouse monoclonal anti-human TNF-a IgG antibody [Saxon Biochemicals (formerly Bissendorf Biochemicals), Hannover, Germany].…”