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Hemodialysis with cuprophane membrane modulates interleukin-2 receptor expression
1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Insights
Dialysis membranes impact immune cells. Cuprophane membranes reduce interleukin-2 (IL-2) receptor expression on lymphocytes, potentially explaining immune deficiency in chronic dialysis patients.
Area of Science:
- Immunology
- Nephrology
- Biomaterials Science
Background:
- Chronic dialysis patients exhibit immune deficiencies.
- Lymphocyte interleukin-2 (IL-2) receptor expression is crucial for cellular immune response.
- Dialysis membrane biocompatibility may affect immune function.
Purpose of the Study:
- To investigate the influence of dialysis membranes on lymphocyte IL-2 receptor expression.
- To determine if cuprophane and polymethylmethacrylate (PMMA) membranes differentially affect immune response.
- To explore the role of blood-membrane interactions in immune deficiency.
Main Methods:
- Cross-over study involving eight chronic hemodialysis patients.
- Comparison of cuprophane and PMMA dialysis membranes.
- Measurement of IL-2 receptor subunits (alpha and beta) on peripheral blood mononuclear cells (PBMC).
- In vitro experiments with PBMC, cuprophane membranes, and C5a anaphylatoxin.
Main Results:
- Cuprophane membrane dialysis increased baseline IL-2 receptor subunit expression (IL2R alpha and IL-2R beta) on PBMC.
- Phytohemagglutinin (PHA) stimulation showed decreased high-affinity IL-2 receptor expression after cuprophane dialysis.
- These effects were reversed with PMMA membranes, which showed minimal complement activation.
- In vitro studies confirmed cuprophane membrane contact and C5a increased IL-2 receptor subunit expression.
Conclusions:
- Dialysis membranes, particularly cuprophane, significantly interact with lymphocytes.
- The observed changes in IL-2 receptor expression may contribute to immune deficiency in dialysis patients.
- PMMA membranes appear more biocompatible, preserving lymphocyte function during dialysis.
Abstract:
Chronic dialysis patients have several indices of immune deficiency. We examined the hypothesis that the biocompatibility of dialysis membranes may influence the ability of lymphocytes to express interleukin-2 (IL-2) receptors on their surface, a key event in cellular immune response. We investigated the potential role of the dialysis membrane in eight chronic hemodialysis patients. The study design was a cross-over study using cuprophane and polymethylmethacrylate (PMMA) membranes. Chronic dialysis with new cuprophane membrane leads to an increase in baseline expression of the two subunits of IL-2 receptors. IL2R alpha (p55, CD25) and IL-2R beta (p70), in peripheral blood mononuclear cell (PBMC). However, Phytohemagglutinin (PHA) stimulation of PBMC harvested after two weeks of dialysis with cuprophane membrane showed a markedly decreased expression of high affinity IL-2 receptors. These findings are reversed when patients were dialyzed with a PMMA membrane which is also associated with minimal complement activation. The increased expression of IL-2 receptor subunits are reproduced in vitro by direct contact of PBMC with cuprophane membrane and by the addition of the anaphylatoxin C5a. This study confirms the participation of lymphocytes in the complex blood-membrane interactions that occurs during dialysis; the results may be relevant to observations of immune deficiency in dialysis patients.