Fish oil infusion reverses 5-fluorouracil-induced impairments in mucosal immunity in mice
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Published on: May 29, 2020
Kazuhiko Fukatsu1, Hidetoshi Nagayoshi, Yoshinori Maeshima
1Division of Traumatology, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. fukatsu@ndmc.ac.jp
Background & Aims:
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.
Methods:
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.
Results:
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.
Conclusion:
Fish oil infusion along with 5FU preserves GALT lymphocyte numbers and respiratory IgA levels.
Insights
Fish oil supplementation can protect the gut immune system from the negative effects of the chemotherapy drug 5-fluorouracil (5FU). This study shows fish oil preserves gut-associated lymphoid tissue (GALT) lymphocytes and respiratory IgA levels during 5FU treatment.
Area of Science:
- Immunology
- Pharmacology
- Gastroenterology
Background:
- Anticancer drugs like 5-fluorouracil (5FU) can weaken the immune system, increasing infection risk.
- Previous research showed 5FU reduces gut-associated lymphoid tissue (GALT) and secretory IgA.
- This study investigates if fish oil can mitigate 5FU's impact on gut immunity.
Purpose of the Study:
- To determine the effect of fish oil on gut mucosal immunity in mice treated with 5FU.
- To assess if fish oil preserves GALT lymphocyte numbers and IgA levels during 5FU chemotherapy.
Main Methods:
- Mice received continuous 5FU infusion, with one group also receiving fish oil emulsion.
- Gut-associated lymphoid tissue (GALT) lymphocytes were isolated from Peyer's patches, intraepithelial, and lamina propria spaces.
- IgA levels in small intestinal, nasal, and broncho-alveolar lavage fluid were measured.
Main Results:
- 5FU treatment significantly reduced intraepithelial and lamina propria lymphocytes and IgA in intestinal and broncho-alveolar lavage fluid.
- Fish oil co-administration restored these lymphocyte counts and IgA levels to those of control mice.
- No significant changes were observed in lymphocyte phenotypes (e.g., CD4, CD8, B220) across groups.
Conclusions:
- Concomitant fish oil infusion with 5FU preserves GALT lymphocyte numbers.
- Fish oil supplementation helps maintain respiratory IgA levels during 5FU treatment.
- Fish oil shows potential as a supportive therapy to mitigate chemotherapy-induced immunodeficiency.
