The Effect and Mechanism of 5-Aminosalicyclic Acid Enema Treatment on Experimental Colitis Induced by a Murine Retrovirus

LP-BM5 murine leukemia virus is known to induce murine acquired immunodeficiency syndrome (MAIDS). We have shown that adoptively transferred spleen cells of MAIDS mice can induce in flammatory bowel disease (IBD)-like colitis, which we termed "MAIDS colitis", in nude mice. Although 5-aminosalicylic acid (5-ASA, mesalazine) is clinically used for successful treatment for IBD, its precise mechanism remains largely unknown. To reveal the effect and mechanism of 5-ASA treatment for our colitis model, four-week-old C57BL/6 (B6) mice were inoculated intraperitoneally with LP-BM5; 8 weeks after infection, lymphnode cells from the mice were transferred into B6 nude mice intraperitoneally to induce MAIDS colitis. The mice were grouped as follows : Group 1,MAIDS colitis mice; Group 2,MAIDS colitis mice treated with only sodium carboxymethylcellulose (CMC) enema; Group 3,MAIDS colitis mice treated with 5-ASA and CMC by enema every day after cell transfer; Group 4,Control B6 nude mice treated with CMC enema. Four to six weeks after cell transfer, 4 mice of each group were killed and the colon was removed for further analyses. The expression of interferon-γ and interleukin-10 protein was detected by a double colorstaining immunofluorescence technique. MAIDS colitis mice showed diarrhea and a bloody stool. Ulcerative colitis (UC)-like colitis lesions were observed histologically, as evidenced by cellular infiltration in the mucosal and submucosal layers crypt abscess and erosions of the colon. In contrast, the number of infiltrating cells was decreased in the colon of MAIDS colitis mice treated with 5-ASA enema. Especially, Mac-1^+ cells (mainly macrophages) and CD4 positive cells that were positive for IFN-γ or IL-10 were reduced in the colon of MAIDS colitis mice undergoing a 5-ASA enema. Colitis did not develop in the control mice. Thus, 5-ASA enema is effective for MAIDS colitis as well as human IBD. One of the therapeutic effects of 5-ASA on IBD might be the suppression of macrophages and CD4^+ T lymphocytes in the colon