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 product ion are a common feature. Their clinical relevance has not yet been pr oven. We show here a correlation between an overproduction of interleu kin- (IL)-6 and tumor necrosis factor alpha (TNF alpha) upon stimulati on with LPS by mononuclear cells in vitro and the clinical grade of im munodeficiency found in these patients. Higher levels of IL-6 and TNF alpha were correlated with an immunocompromized state, that is, non re sponsiveness to hepatitis B vaccination, whereas patients with a batte r immune competence showed the same levels of these cytokines as healt hy controls. Only the patients with a good immune function showed a hi gh secretion of IL-10. The feedback mechanism of IL-10 for reducing mo nokine synthesis seems to be intact in these patients. Thus the secret ion of IL-10 might be regarded as a compensatory mechanism which contr ols monokine induction by chronic renal failure and hemodialysis treat ment. Immunocompromized patients who are unresponsive to hepatitis B v accination seem to be unable to enhance IL-10 synthesis for control of monokine overproduction. This results in higher levels of IL-6 and TN F alpha that might be involved in the pathogenesis of reduced immune d efense.