Induction of Cytokines by Dialysis Membranes in Normal Whole Blood: A New in vitro Assay for Evaluating Membrane Biocompatibility

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Abstract
We investigated the capacity of cellulose cuprophane (CUP) and synthetic polyacrylonitrile dialysis membranes to induce the production of interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha using an in vitro model in which normal whole blood is incubated directly with calibrated membrane fragments. We found that only CUP membranes significantly increased plasma levels of IL-1, IL-6, and tumor necrosis factor alpha. The participation of lipopolysaccharide was excluded, since its addition to whole blood incubated with CUP led to a synergistic enhancement of IL-1 production, while the addition of polymyxin B had no significant effect. Transfer experiments showed that CUP-pretreated plasma was able to induce cytokine production by autologous monocytes. Inactivation of complement components prior to pre-treatment abolished this effect. The participation of complement activation was further revealed by a correlation between cytokine and C5a plasma levels. Lastly, incubation of isolated monocytes with CUP but not with polyacrylonitrile also induced cytokine production, although to a lesser degree. In conclusion, our simple in vitro model can be used to evaluate the biocompatibility of dialysis membranes directly by using whole blood with greater relevance to the in vivo situation than models based on isolated blood components.

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