5-Fluorouracil Infusion Reduces Gut-Associated Lymphoid Tissue Cell Number and Mucosal Immunoglobulin A Levels

Abstract

Background: Anticancer drugs have been demonstrated to affect gut mucosal morphology and cause gastrointestinal symptoms. We hypothesized that even small doses of 5-fluorouracil (5-FU) would reduce gut-associated lymphoid tissue (GALT) mass and function. Methods: Mice underwent IV cannulation and received continuous infusion of normal saline or 10 mg/kg of 5-FU for 5 days. GALT cell numbers, phenotypes, and mucosal immunoglobulin A (IgA) levels were measured. Results: During the infusion, there were no significant differences in food intake or body weight change between the 2 groups. Cell yields from the intraepithelial space and lamina propria of the small intestine were lower in the 5-FU than the control group. The lamina propria CD4/CD8 ratio was reduced in the 5-FU compared with the control group. Intestinal and respiratory tract IgA levels were lower in the 5-FU than in the control group. Conclusions: A small dose of 5-FU reduces GALT cell number and mucosal IgA levels, regardless of food intake.

Mice received continuous IV infusion of normal saline or 10 mg/kg of 5-fluorouracil (5-FU) for 5 days. Despite no differences in body weight changes or food intake, gut-associated lymphoid tissue cell numbers and mucosal IgA levels were lower in the 5-FU than the control group.