Suppressive effects of cyclosporine A on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant ulcerative colitis.
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-1alpha 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.
Ina
Kenji
K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kusugami
Kazuo
K
Shimada
Masaaki
M
Tsuzuki
Tomoyuki
T
Nishio
Yuji
Y
Binion
David G
DG
Imada
Akira
A
Ando
Takafumi
T
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D019804:Mesalamine / Q000494:pharmacology* / Q000627:therapeutic use; D009504:Neutrophils / Q000187:drug effects*; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D013491:Suppressor Factors, Immunologic / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D013491:Suppressor Factors, Immunologic; D019804:Mesalamine; D016572:Cyclosporine; D011239:Prednisolone