Elevated circulating levels of interleukin-6 in patients with chronic renal failure

Elevated circulating levels of interleukin-6 in patients with chronic renal failure. In a previous study, we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term dialyzed patients and that of tumor necrosis factor alpha (TNFα) in both long-term and not yet dialyzed uremic patients. In the present study, we attempted to determine the respective influence of hemodialysis (HD) and uremia on the plasma level of interleukin-6 (IL-6), which shares several biological properties with IL-1 and TNFα, including the induction of the acute phase response of the inflammatory processForty-eight patients with end-stage renal failure, including 32 long-term HD patients and 16 chronic uremic patients undergoing their first dialysis session, were tested forplasma IL-6 using both biological and immunoreactive assays. Plasma IL-6 activity was significantly increased in patients with chronic renal failure (P < 0.001) compared to its level in normal individuals. No difference was observed, however, between long-term and not yet dialyzed patients. In the patients with the most pronounced IL-6 activity, immunoreactive IL-6 levels between 60 and 150 pg/ml were detected. A monoclonal antibody (mAb) against human IL-6 inhibited the activity of plasma in the IL-6 bioassay, and a close correlation existed between the biological activity of IL-6 and its immunoreactive level. No change in plasma IL-6 was detected during the course of the first dialysis as well as subsequent sessions. Likewise, no influence of the nature (cellulosic or synthetic polyacrilonitrile) of the dialysis membrane equipping the dialyzer was observed. However, compared to predialysis levels, a significant increase in plasma IL-6 was measured four hours following the end of the dialysis session in long-term HD patients, thus contrasting with the relative decrease measured in first-dialyzed patients. Lastly, in long-term HD patients, there was a significant correlation between maximum plasma IL-6 (measured 4hr postdialysis) and maximum plasma IL-1 (measured at the end of the dialysis session). From these results, we conclude that uremia per se is the principal origin of increased plasma IL-6 and that factors related to repeated dialysis procedure including IL-1 may contribute in maintaining increased plasma levels of IL-6