CAM--a novel immunosuppressive agent.
This is an initial study of the immunosuppressive efficacy of CAM, a derivative of mycophenolic acid, in a rat heart allograft model when the major histocompatibility complex was fully incompatible, and its effect in improving heart allograft survival compared with mycophenolate mofetil (MMF, RS-61443). CAM or MMF was administered orally from day 1 following the allografting for 40 days. The median survival times (MST) were 6 days in rats with no immunosuppressive drug (control group; n = 6), 83 days with CAM 10 mg/kg (n = 6), and > 100 days with both 20 mg/kg (n = 7), and 30 mg/kg (n = 10). With MMF, in contrast, MST was 9, 17, 35, days with 10, 20, 30 mg/kg/day, respectively. All grafts in the CAM 30 mg/kg-treated group survived for more than 100 days after grafting, and, furthermore, CAM was also more effective than MMF in prolongation of the heart graft survival in rats at each dose. Rats with long-surviving cardiac allografts (30 mg/kg; CAM) accepted skin grafts from the donor-strain but rejected them from the third-party strain, suggesting that donor-specific tolerance was induced by CAM. In the tolerant rats, proliferative response against donor-type alloantigen was not impaired as compared with naive WKAH rats. In contrast, CML assay showed that T cells obtained from the rats bearing permanently accepted F344 heart grafts had less cytotoxic activity to the donor-type target, and the frequency of CTL precursor against donor-type alloantigen was also reduced.
Takazawa
K
K
Department of Cardiothoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Hosoda
Y
Y
Bashuda
H
H
Yagita
H
H
Okumura
K
K
Kaneko
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; C031864:ethyl O-(N-(4-carboxyphenyl)carbamoyl)mycophenolate; D009173:Mycophenolic Acid