Interleukin-6 in CAPD patients without peritonitis: Relationship to the intrinsic permeability of the peritoneal membrane

We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected all 'nightbags' on consecutive days during 2 months for the determination of peritoneal IgG clearance. Serum samples were obtained weekly. IL-6 was determined in the effluent on all occasions where the IgG clearance was < x̄ - SD or > x̄ + SD. On these days clearances of β₂-microglobulin, albumin and α₂-macroglobulin were determined as well, to calculate the peritoneal restriction coefficient, i.e. the slope of the power relationship between protein clearances and their free diffusion coefficient in water. This coefficient was used as a parameter of the intrinsic permeability of the membrane. IL-6 was measured by a sensitive and specific bioassay, using the B13.29, subclone 9.9 hybridoma cell assay. Dialysate IL-6 was measured on 43 occasions when IgG clearance was high and on 37 occasions when IgG clearance was low. In all 4 patients indirect evidence was found for local production of IL-6 within the peritoneal cavity: mean dialysate/serum ratios were 15 to 452 times higher than could be expected when IL-6 would enter the dialysate by diffusion only. The patient with the highest dialysate/serum ratio showed higher clearances of albumin, IgG and α₂-macroglobulin than the other 3 patients (p <0.001) and a lower restriction coefficient (p <0.001), indicating a high intrinsic permeability. Dialysate IL-6 was not normally distributed: 12 outliers exceeding the upper level of normal distribution could be identified. These outliers were associated with significantly higher clearances of albumin (p = 0.039), IgG (p = 0.005) and α₂-macroglobulin (p = 0.002), than on days when IL-6 was within the normal distribution. The outliers also showed lower restriction coefficients (p = 0.002), whereas no difference was found for β₂-microglobulin clearance, used as an indicator of effective peritoneal surface area. It is concluded that IL-6 can be produced locally within the peritoneal cavity in stable CAPD patients without infection. Very high dialysate IL-6 concentrations were associated with increased intrinsic permeability of the peritoneum, but not with the effective surface area.