ZINC REGULATES DNA-SYNTHESIS AND IL-2, IL-6, AND IL-10 PRODUCTION OF PWM-STIMULATED PBMC AND NORMALIZES THE PERIPHERE CYTOKINE CONCENTRATION IN CHRONIC LIVER-DISEASE

Zinc (zinc ions and/or chelated zinc) plays an important role in the m aintenance of immune function. Patients with chronic liver disease, pa rticularly liver cirrhosis, frequently have endotoxemia, increased ser um concentrations of cytokines, e.g., interleukin-6 (IL-6), and reduce d serum zinc levels. The aim of the present study was to investigate t he effects of zinc (ZnCl2, ZnO, ZnSO4) on DNA synthesis and cytokine p roduction (IL-2, IL-6, IL-10) in pokeweed mitogen (PWM)-stimulated per ipheral blood mononuclear cells (PBMC). In addition, we examined the e ffect of long-term zinc supplementation (zinc-hydrogen-aspartate; UNIZ INK 50; 3 x 1 = 29.76 mg/day) on IL-6 and IL-10 serum levels in patien ts with chronic liver disease (n = 16), all with reduced serum zinc le vels. It could be shown that zinc concentrations up to 0.1 mM stimulat e DNA synthesis and cytokine production by PWM-stimulated PBMC, wherea s higher concentrations (0.2-0.4 mM) have a strongly inhibitory effect . Zinc concentrations exceeding 0.5 mM were found to have a toxic effe ct on these immune cells. Interestingly, in most patients with chronic liver disease (n = 10), zinc supplementation decreased IL-6, and to a lesser extent, IL-10 serum levels, and normalized the serum zinc conc entrations. We conclude that zinc plays a regulatory role in DNA synth esis and cytokine production by PBMC. The critical zinc concentration for immune cells lies in the range of 0.5 mM, which is equivalent to a daily dose of similar to 45 mg zinc salt. Furthermore, zinc supplemen tation in chronic liver disease with reduced serum zinc levels appears to normalize IL-6 and IL-10 production. (C) 1997 Wiley-Liss, Inc.