Fish oil infusion reverses 5-fluorouracil-induced impairments in mucosal immunity in mice

Abstract

Anticancer drugs frequently have deleterious effects on host defense against infection, limiting their clinical application. We previously demonstrated continuous infusion of 5-fluorouracil (5FU) to reduce gut associated lymphoid tissue (GALT) mass and secretory IgA levels. This study was designed to examine the effects of concomitant infusion of fish oil on gut mucosal immunity in mice receiving 5FU. Male ICR mice were randomized to the control (n=12), 5FU (n=12), or 5FU+FO (n=10) group. The 5FU and 5FU+FO groups received continuous IV infusion of 5FU at 10 mg/kg for 5 days. The 5FU+FO group was given a simultaneous infusion of 10 ml/kg of a 10% fish oil emulsion. The controls received normal saline at 0.3 ml/h. During these treatments, all mice were allowed free access to chow and water ad libitum. Then, the mice were sacrificed and GALT lymphocytes were isolated from Peyer's patches (PPs), the intraepithelial space (IE), and the lamina propria (LP). Small intestinal, nasal and broncho-alveolar (BALF) washings were also obtained. Lymphocyte yields from each site and phenotypes (CD4, CD8, alphabetaTCR, gammadeltaTCR, B220) were determined. IgA levels in the washings were measured with ELISA. The 5FU group had significantly lower IE and LP lymphocyte numbers and small intestinal and BALF IgA levels than the control group, with no differences in the percentages of any phenotypes. However, fish oil infusion restored IE and LP lymphocyte numbers and BALF IgA to control group levels. Fish oil infusion along with 5FU preserves GALT lymphocyte numbers and respiratory IgA levels.