Immune Dysfunction and Cytokine Production in Hemodialysis

Abstract

Most uremic patients in dialysis therapy develop an immunodeficiency characterized clinically by frequent infectious complications and impaired response to vaccinations [1]. This became evident in the early period of hemodialysis treatment when endemic outbreaks of hepatitis B threatened dialysis centers [2]. Vaccination results against hepatitis B, in dialysis patients, are disappointing: low results are also documented for most other types of vaccinations in these patients, such as influenza [3], tetanus [4] or diphteria [5]. There is an only exception in using vaccination containing polysaccharide antigens like pneumococcus [6]. Polysaccharide antigens are recognized by B cells on their own, but for recognition of other antigens, B cells need specific T-cell help: these observations indicate that the major defects appear to be in cellmediated immunity [7–9] and in particular correlated to T-cell rather than B-cell function [10]. In normal conditions, in response to antigens, naive CD4+ T cells differentiate into effector T helper (Th) cells. Based on their pattern of cytokine production and their functional responses, Th cells can be subdivided into those that participate in cell-mediated immune responses such as delayed type of hypersensitivity reactions and macrophage activation (Th1 subset) and those releasing cytokines that induce B cells to secrete antibodies (Th2 subset). Several factors are known to polarize the differentiation of Th cells into either Th1 or Th2 direction, including the co-stimulatory action of antigen presenting cells (APCs), the cytokine environment, altered peptide ligands and the antigen dose. In particular, Th1 are characterized by elevated secretion of interleukin (IL)-2, transforming growth factor-s (TGF-s) and interferon-A (IFN-A), thereby activating cytotoxic T lymphocytes and macrophages. Moreover, IFN-A suppresses Th2 which induces humoral immunity. The Th2 subset of CD4+ T cells preferentially secretes IL-4, IL-5, IL-6 and IL-10 [11– 13], stimulating the proliferation of mast cells and eosinophils as well as the production of immunoglobulins and IL-10 which may suppress the Th1-induced cell-mediated immunity [14, 15]. In general, Th1 cytokines promote Th1 and inhibit Th2 activities and vice versa. Th1 and Th2 responses should, therefore, be stable [16]. Chronic renal failure induces a clinical state of immunodeficiency in most patients: immune defects may be caused by uraemic state itself and by a direct consequence of dialytic therapy [17, 18]. Dialysis has been associated with acute changes in the complement activation status, granulocyte markers, macrophage function, T-cell activation and the release of various pro-inflammatory cytokines. Although the physiolog-