Suppressive effects of cyclosporine A on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant ulcerative colitis
Kenji Ina
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Dr. Kazuo Kusugami
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466–8550, JapanSearch for more papers by this authorMasaaki Shimada
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorTomoyuki Tsuzuki
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorYuji Nishio
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorDavid G. Binion
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.
Search for more papers by this authorAkira Imada
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorTakafumi Ando
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorKenji Ina
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Dr. Kazuo Kusugami
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466–8550, JapanSearch for more papers by this authorMasaaki Shimada
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorTomoyuki Tsuzuki
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorYuji Nishio
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorDavid G. Binion
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.
Search for more papers by this authorAkira Imada
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorTakafumi Ando
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Search for more papers by this authorAbstract
An intravenous infusion of cyclosporine A (CsA) shows clinical benefits in patients with steroid-resistant ulcerative colitis (UC). To clarify its mechanisms, we investigated the ability of CsA to inhibit the functions of neutrophils and T cells. The cytotoxic activity by mucosal T cells was analyzed by anti-CD3-triggered cytotoxicity after lamina propria mononuclear cells were cultured with recombinant interleukin (IL)-2. The chemotactic response, the generation of superoxide, and the production of chemokines, IL-8, and macrophage inflammatory protein-1α by neutrophils were examined using a multiple-well chamber assay, a chemiluminescence method, and an enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal chemokine activity was determined by an ELISA using the organ culture supernatant of mucosal biopsy tissues. Pretreatment with CsA caused consistent inhibitions of cytotoxic activity by mucosal T cells and chemotactic migration, superoxide generation, and chemokine production by neutrophils mostly in a dose-dependent manner. In patients who received an intravenous infusion of CsA, mucosal chemokine activity decreased after therapy in parallel with decreases in the numbers of neutrophils and mononuclear cells in the biopsy tissues. These results suggest that suppressive effects of CsA on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant UC.
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