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

Yoshihisa Yaguchi, MD^*, Kazuhiko Fukatsu, MD, Tomoyuki Moriya, MD, Yoshinori Maeshima, MD^*, Fumie Ikezawa, MD, Jiro Omata, MD^*, Chikara Ueno, MD^*, Koichi Okamoto, MD^*, Etsuko Hara, MD, Takashi Ichikura, MD^*, Hoshio Hiraide, MD and Hidetaka Mochizuki, MD^*

From the ^* Department of Surgery I, National Defense Medical College, Tokorozawa, Japan; Division of Basic Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan; and the Department of Surgery I, Chiba University, Chiba, Japan

Correspondence: Kazuhiko Fukatsu, MD, Division of Basic Traumatology, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama, Japan 359-8513. Electronic mail may be sent to fukatsu{at}ndmc.ac.jp.

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 x 2), and control (saline 0.1 mL x 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, βTCR, TCR, 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.

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New Jersey University of Medicine & Dentistry

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