Influences of Long-Term Antibiotic Administration on Peyer's Patch Lymphocytes and Mucosal Immunoglobulin A Levels in a Mouse Model

Abstract

Background: Long-term antibiotic administration is sometimes necessary to control bacterial infections during the perioperative period. However, antibiotic administration may alter gut bacterial flora, possibly impairing gut mucosal immunity. We hypothesized that 1 week of subcutaneous (SC) antibiotic injections would affect Peyer's patch (PP) lymphocyte numbers and phenotypes, as well as mucosal immunoglobulin A (IgA) levels. Methods: Sixty-one male Institute of Cancer Research mice were randomized to CMZ (cefmetazole 100 mg/kg, administered SC twice a day), IPM (imipenem/cilastatin 50 mg/kg × 2), and control (saline 0.1 mL × 2) groups. After 7 days of treatment, the mice were killed and their small intestines removed. Bacterial numbers in the small intestine were determined using sheep blood agar plates under aerobic conditions (n = 21). PP lymphocytes were isolated to determine cell numbers and phenotypes (CD4, CD8,αβ TCR, γδTCR, B220; n = 40). IgA levels in the small intestinal and bronchoalveolar washings were also measured with ELISA. Results: Antibiotic administration decreased both bacterial number and the PP cell yield compared with the control group. There were no significant differences in either phenotype percentages or IgA levels at any mucosal sites among the 3 groups. Conclusions: Long-term antibiotic treatment reduces PP cell numbers while decreasing bacterial numbers in the small intestine. It may be important to recognize changes in gut mucosal immunity during long-term antibiotic administration.

We studied influences of 7 days’ treatment of cefmetazole and imipenem/cilastatin on gut immunity in a mouse model. As compared with saline-treated controls, antibiotics reduced lymphocyte number in Peyer’s patches, the inductive site of mucosal immunity, while decreasing bacterial numbers in the small intestine.