Production of monokines in patients under polysulphone haemodiafiltration is influenced by the ultrafiltration flow rate

Background. Chronic haemodialysis patients show various clinical signs of i mmunodeficiency and there is growing evidence that a dysregulated monocyte cytokine, production is heavily involved in this deficiency. The production of monokines in vitro has been proposed to correlate closely with the in v ivo immune status and to be of high clinical relevance in cuprophane haemod ialysis. Even though it is well known that the biocompatibility of dialyser membranes has a significant impact on immune functions, little is known ab out the influence of the ultrafiltration flow rate (UFR). The aim of this s tudy was to investigate the potential long-term effects of UFR on the produ ction of interleukin-10 (IL-10), interleukin-1 beta (IL-1 beta) and interle ukin-6 (IL-6) in an intra-individual study design. Methods. In I I patients previously treated with polysulphone haemodiafiltr ation, UFR was reduced from 40-46 ml/min to 24-28 ml/min, then to 7-10 ml/m in before it was reinstated at 40-46 ml/min for periods of 4 weeks each. Mo nokine secretion into culture supernatants. and mRNA expression (assessed u sing a novel Taqman PCR technique), were determined in a whole blood assay after lipopolysaccharide stimulation. Results. Reduction of UFR led to a significant increase in IL-10 secretion and mRNA expression (P=0.012, P=0.001). Conversely, a substantial (but not complete) decrease was observed when UFR returned to initial levels. In con trast, supernatant concentrations of IL-1 beta (P=0.04) and IL-6 (P=0.003), and mRNA expression of both monokines (P <0.001, P <0.001) decreased signi ficantly when UFR was reduced. Calculation of the IL-1 beta /IL-10 ratio al so revealed a decrease when UFR was reduced, with an increase again being o bserved when the initial degree of UFR was reinstated (P <0.001). Conclusions. These results indicate a significant impact of UFR on the prod uction of monokines at both the transcriptional and the protein level. We s uggest that middle molecule removal has to be considered as a possible path ophysiological mechanism to explain our findings. Since monokine production in vitro was shown to be closely correlated with the in vivo immune status in patients on cuprophane haemodialysis, further investigations are necess ary to clarify the impact of UFR on the immunocompetence of patients under polysulphone haemodiafiltration.