ROLE OF THE LOW ZINC BIOAVAILABILITY ON CELLULAR IMMUNE EFFECTIVENESSIN CYSTIC-FIBROSIS

An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to e radicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence o f other cellular immune defects and their cause. Alterations in zinc t urnover are present in CF. Zinc is relevant for good immune functionin g. In particular, zinc is required to confer biological activity to th ymulin (ZnFTS), a biochemically defined thymic hormone with a modulati ng action on cell-mediated immunity. The zinc-unbound form (FTS) is in active and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + i nactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fraction s in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plas ma levels of inactive thymulin compared to the values of healthy child ren (P < 0.01). A strict correlation exists between zinc and thymic ho rmone-saturable fraction (r = 0.87, P < 0.01) in CF. These findings su ggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depe nd on augmented plasma concentration of alpha(2)-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets a re normal in CF. Reduced NK cell number and activity are present. Also , plasma IL-2 levels are reduced. The existence of positive correlatio ns between zinc and IL-2 (r = 0.79, P < 0.01) and between zinc or acti ve thymulin and NK activity (r = 0.70, P < 0.01 and r = 0.88, P < 0.01 , respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a comple te saturation of thymulin molecules, to correct some cellular immune d efects and to improve the growth, may be suggested. (C) 1995 Academic Press, Inc.