INVOLVEMENT OF INTERLEUKIN-1-BETA IN ZINC DEFICIENCY-INDUCED INTESTINAL DAMAGE AND BENEFICIAL EFFECT OF CYCLOSPORINE-A

In a previous study we have shown that zinc deficiency caused several alterations in intestine of rats. Here we report that interleukin-1 be ta (IL-1 beta) is involved in the zinc deficiency-induced mucosal dama ge and that cyclosporine A (CsA) protects the intestine against both s tructural and functional alterations by different mechanisms. The zinc deficient (ZD) rats were maintained on a zinc deficient diet for 40 d ays. They received a daily injection of CsA (12 mg/kg) for the last 10 days. The histological analysis of small intestine revealed that the dramatic alterations induced by zinc deficiency (ulcerations, inflamma tion, edema, vasodilatation), were not present after CsA treatment. Th e IL-1 beta gene expression, analyzed by PCR, was increased in the thr ee intestinal regions of ZD rats, as compared to C rats. There was a r elation between increasing IL-1 beta expression and increased severity of damage, and the highest cytokine elevation was in the most damaged region, i.e. the jejunum. After CsA administration the IL-1 beta mRNA was similar to control rats. The intestinal cell proliferation, measu red as crypt cell production rate and labelling index, as well the cel l renewal, measured as cell migration rate and turnover time, were aff ected by zinc deficiency. After CsA treatment, all these variables wer e similar to control rats, suggesting that CsA induces a stimulation o f intestinal cell proliferation in zinc deficiency. Finally, the decre ase in the disaccharidase activities induced by zinc deficiency was ab rogated by CsA treatment.