Alcohol-Induced Immune Dysregulation in the Colon Is Diurnally Variable.

INTRODUCTION

Alcohol increases the risk of colon cancer. Colonic inflammation mediates the effects of alcohol on colon carcinogenesis. Circadian rhythm disruption enhances the alcohol's effect on colonic inflammation and cancer.

OBJECTIVE

Here, we investigate the diurnal variation of lymphocyte infiltration in the colonic mucosa in response to alcohol.

METHODS

Sixty C57BL6/J mice were fed a chow diet, and gavaged with alcohol at a specific time once per day for 3 consecutive days. Immunohistochemistry and immunofluorescence staining were used to quantify total, effector, and regulatory T cells in the colon. Student's test, one-way ANOVA, and two-way ANOVA were used to determine significance.

RESULTS

Following the alcohol binge, the composition of immune T cell subsets in the mouse colon was time-dependent. Alcohol did not alter the total number of CD3 T cells. However, upon alcohol treatment, T-bet T helper 1 (Th1) cells appeared to dominate the T cell population following a reduction in Foxp3 regulatory T cell (Treg) numbers. Depletion of Tregs was time-dependent, and their numbers were dramatically reduced when alcohol was administered during the rest phase. A reduction in Tregs significantly increased the Th1/Treg ratio, resulting in a more proinflammatory milieu.

CONCLUSIONS

Alcohol enhanced the proinflammatory profile in the colon mucosa, as demonstrated by a higher T-bet/Foxp3 ratio, especially during the rest phase. These findings may partly account for the interaction of circadian rhythm disruption with alcohol in colon inflammation and cancer.