No abstract

Chronic renal failure is associated with severe alterations of the immune system. Infections are responsible for a large part of the mortality in hemodialysis patients, and vaccination is mostly ineffective. Global tests of the immune function show greatly diminished activation of T cells. However, the intrinsic function of T and B cells is normal when they are provided with normal signaling from antigen-presenting cells (APCs). Patients with chronic renal failure show a defective function of costimulation derived from APCs leading to impaired activation of effector lymphocytes. Two major components of immune deviation are relevant: reduced signaling caused by impaired expression of the costimulatory molecule B7-2 (CD86) on monocytes leads to low activation of helper T cells. This dysfunction is associated with uremia and may be improved by high-efficiency renal replacement therapy. The other component is inflammatory activation of APCs mainly due to the hemodialysis procedure. Inflammation, characterized by overproduction of cytokines such as interleukin-1beta (IL-1beta) or IL-6, correlates with low effector activation. Furthermore, inflammatory cytokines such as IL-12 deviate the functional pattern of T-cell activation toward Th1 differentiation, thus leading to an additional reduction of Th2- and B-cell function. The individual severity of inflammatory alterations is partially controlled by the negatively regulating cytokine IL-10, which, on a genetic basis, can be up-regulated to a different extent in individual patients. Therapeutic interventions to improve immune dysfunction include the enhancement of dialysis efficiency and the reduction of inflammatory alterations by the use of highly biocompatible dialyzers.

Our findings contribute to a better understanding of the pathogenesis of impaired cellular immune functions in dialysis patients and, in particular, the decreased antibody production after vaccination. They provide a link between overproduction of pro-inflammatory cytokines (IL-12) and imbalanced T-cell activation.

No abstract

The IL-10 genotype influences the risk for cardiovascular events in hemodialysis patients and allows the definition of a high risk group. The data provide further evidence for a causal role of systemic inflammation for progressive atherosclerosis in dialysis patients.