Humoral immune responses in uremia and the role of IL-10

Abstract

Chronic renal failure severely influences the immune functions of the host. Recent work has shown that uremic intoxication as well as its treatment alters distinct aspects of immunity and that the organism has certain mechanisms to compensate, at least in part, for these influences. Failure of the humoral branch of immune function becomes apparent when vaccinations are applied to the dialysis patient. Severely impaired vaccine responses are common, particularly against hepatitis B, tetanus, or influenza. In contrast, patients with chronic renal failure may develop adequate humoral responses against vaccines such as pneumococcus. The degree of impairment of humoral responses is related to the antigen's dependence on T-helper lymphocyte activation, which is high for hepatitis or influenza, and low for large polysaccharide antigens. T-helper cell activation on the other hand is greatly influenced by inflammatory processes, e.g. the secretion of cytokines such as interleukin (IL-)-1 or IL-6. These inflammatory processes are induced by uremic toxins and contacts between blood and extracorporeal surfaces of the dialysis equipment. They are subject to the body's compensatory mechanisms for inflammation, which are mainly based on the anti- inflammatory cytokine IL-10. Genetically determined differences in the secretion capacity for this compensatory cytokine strongly influence humoral immunity in the patient with chronic renal failure and thus allow the definition of a high-risk group for infection and vaccine nonresponse.