PRODUCTION OF INTERLEUKIN-6, TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-10 IN-VITRO CORRELATES WITH THE CLINICAL IMMUNE DEFECT IN CHRONIC-HEMODIALYSIS PATIENTS

In patients with chronic renal failure alterations in monokine production are a common feature. Their clinical relevance has not yet been proven. We show here a correlation between an overproduction of interleukin- (IL)-6 and tumor necrosis factor alpha (TNF alpha) upon stimulation with LPS by mononuclear cells in vitro and the clinical grade of immunodeficiency found in these patients. Higher levels of IL-6 and TNF alpha were correlated with an immunocompromized state, that is, non responsiveness to hepatitis B vaccination, whereas patients with a batter immune competence showed the same levels of these cytokines as healthy controls. Only the patients with a good immune function showed a high secretion of IL-10. The feedback mechanism of IL-10 for reducing monokine synthesis seems to be intact in these patients. Thus the secretion of IL-10 might be regarded as a compensatory mechanism which controls monokine induction by chronic renal failure and hemodialysis treatment. Immunocompromized patients who are unresponsive to hepatitis B vaccination seem to be unable to enhance IL-10 synthesis for control of monokine overproduction. This results in higher levels of IL-6 and TNF alpha that might be involved in the pathogenesis of reduced immune defense.