Intraperitoneal IL-6 signaling in incident patients treated with icodextrin and glucose bicarbonate/lactate-based peritoneal dialysis solutions.

Abstract

OBJECTIVE:

In this study, we compared the activity of interleukin-6 (IL-6), a marker of ongoing peritoneal inflammation and biocompatibility, and its other signaling components, the soluble IL-6 receptor (sIL-6R) and soluble Gp130 (sGp130), in peritoneal effluent from patients treated with icodextrin-based (E) peritoneal dialysis (PD) solution and glucose-based bicarbonate/lactate-buffered (P) solution.

METHODS:

Using baseline peritoneal ultrafiltration capacity, 33 stable incident PD patients were allocated either to P only (n = 20) or to P plus E for the overnight dwell (n = 13). We used ELISA to determine IL-6, sIL-6R, and sGp130 in timed overnight effluent at 1, 6, and 12 months after PD initiation. Flow cytometry was used to measure expression of IL-6R and Gp130 on isolated peritoneal leukocytes at the same time points. Peritonitis was an exclusion criterion.

RESULTS:

At all time points, levels of IL-6 and sIL-6R, and the appearance rates of IL-6 (90.5 pg/min vs. 481.1 pg/min, p < 0.001; 138.6 pg/min vs. 1187.5 pg/min, p < 0.001; and 56.1 pg/min vs. 1386.0 pg/min, p < 0.001), sIL-6R (2035.3 pg/min vs. 4907.0 pg/min, p < 0.01; 1375.0 pg/min vs. 6348.4 pg/min, p < 0.01; and 1881.3 pg/min vs. 5437.8 pg/min, p < 0.01), and sGp130 (37.6 ng/min vs. 65.4 ng/min, p < 0.01; 39.2 ng/min vs. 80.6 ng/min, p < 0.01; 27.8 ng/min vs. 71.0 ng/min, p < 0.01) were significantly higher in peritoneal effluent from E-treated patients than from P-treated patients. Expression of IL6-R and Gp130 on individual leukocyte types isolated from PD effluent did not differ between E- and P-treated patients. The numbers of white blood cells present in effluent were higher in E-treated than in P-treated patients at all time points, but no significant differences were seen in the differential counts or in the number of exfoliated mesothelial cells. The IL-6 parameters in effluent from E-treated patients correlated with their plasma C-reactive protein. Despite the increased activation of the IL-6 system, no increase in peritoneal permeability as assessed by the dialysate-to-plasma ratio of creatinine in E effluent or by systemic inflammation was observed throughout the study.

CONCLUSIONS:

Higher levels of IL-6, its soluble receptors, and leukocyte expression were observed in E-treated than in P-treated patients, but this difference was not associated with alterations in peritoneal permeability or systemic inflammation during 1 year of follow-up. Leukocyte counts in effluent from E-treated patients were within the normal range previously reported for glucose solutions. This lack of clinical consequences may be a result of a parallel rise in sIL-6R and sGp130, which are known to control the biologic activity of IL-6. The utility of IL-6 level determinations, in isolation, for assessing the biocompatibility of PD solutions is questionable.

• Authors: Sylvie Opatrna, Daniel Lysak, Ladislav Trefil, Clare Parker, Nicholas Topley
• Journal: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis (Perit Dial Int) 2012 Jan-Feb Vol. 32 Issue 1 Pg. 37-44 ISSN: 1718-4304 [Electronic] United States
• PMID: 22302924 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bicarbonates
• Dialysis Solutions
• Drug Combinations
• Glucans
• Interleukin-6
• Icodextrin
• Lactic Acid
• Glucose

Topics

• Adult
• Aged
• Bicarbonates (pharmacology)
• Dialysis Solutions (pharmacology)
• Drug Combinations
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Follow-Up Studies
• Glucans (pharmacology)
• Glucose (pharmacology)
• Humans
• Icodextrin
• Interleukin-6 (metabolism)
• Lactic Acid (pharmacology)
• Male
• Middle Aged
• Peritoneal Dialysis, Continuous Ambulatory (methods)
• Peritoneum (drug effects, metabolism, pathology)
• Prospective Studies
• Signal Transduction
• Time Factors
• Young Adult