A low zinc concentration detected in sera under zinc deficiency induces dysregulation of cytokine productions in rats

Abstract

Zinc (Zn) deficiency has been observed in patients with ulcerative colitis (UC), although the precise contribution of Zn to UC prevetion has not been elucidated until now. We investigated Zn status during dextran sulfate sodium (DSS) ‐ induced colitis. Rats were fed Zn adequate diet (ZA, 30 mg Zn/kg diet) as a control or Zn deficient diet (ZD, 5 mg Zn/kg diet) for 21 days and then treated with 2% DSS through deionized drinking water for 7 days. The disease activity index (DAI) was recorded daily during the DSS treatment. Serum Zn concentration in the rats fed the ZD diet was significantly lower than in those fed the ZA diet at day‐7 and ‐ 14. DSS treatment considerably reduced the serum Zn to the same extent in both groups. The ZD rats showed exacerbated colitis as assessed by clinical outcomes including weight loss, increased DAI, and shortening of colon length. In vitro study corroborated these results, showing that large amounts of TNFα were produced under ZD medium by rat mesenteric leukocytes in response to stimulants. Interestingly, such increase in the TNFα production was not found under ZA medium. These results indicate that excess TNFα production due to Zn deficiency increases the disease activity in DSS‐induced colitic rats.