The transfer of cytokine-inducing substances across high-flux membrane dialyzers.
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The transfer of cytokine-inducing substances (CIS) or endotoxin (ET) fragments across high-flux membrane (EVAL, PAN, and PMMA) dialyzers was studied using culture media contaminated with Pseudomonas aeruginosa isolated from our dialysate delivery system. Production of cytokines (IL-1β, IL-6 and TNFα) by peripheral blood monocytes was assayed during subsequent 20-hour culture in backfiltrate media prepared with selected high-flux membrane dialyzers. No penetration of CIS across high-flux membrane dialyzers was seen when culture media containing clinically relevant or even higher concentrations of ET (621pg/ml-100ng/ml) were used as a challenge. Transfer of CIS was clearly demonstrated, however, only when a culture medium with irrelevant ET (8.92μg/ml) contamination was used as the challenge.In another series of experiments, cytokine production by monocytes was studied before and after simple extracorporeal recirculation of whole blood for 3 hours, using a polyacrylonitrile (PAN) hollow-fiber high-flux hemodialyzer to see whether or not the ex vivo circulation itself might play some role as a cytokine-inducer. No change in cytokine production was seen before or after the extracorporeal circulation. The effect of C5a was also examined in terms of cytokine induction. No cytokine induction was demonstrated in the presence of C5a (100ng/ml) alone, but C5a had a significant effect in terms of producing more cytokines when incubated with LPS.The results show that the penetration of CIS across dialyzer membranes may be restricted to extreme situations such as clinically irrelevant ET contamination (μg/ml range). Furthermore, C5a may act as a primer to stimulate cytokine production in the presence of ET, but neither extracorporeal circulation alone nor C5a itself seems to be enough to induce cytokine production and release from monocytes.
- 社団法人 日本透析医学会の論文
社団法人 日本透析医学会 | 論文
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