The impact of FK506 on graft coronary disease of rat cardiac allograft--a comparison with cyclosporine.
We studied the impact of FK506, a potent immunosuppressant, on graft coronary disease and graft-infiltrating lymphocyte subset after rat heart transplantation. Fisher rat heart grafts transplanted into Lewis rat recipients were divided into three groups: control (n = 7), rats treated with FK506 at a dose of 0.32 mg/kg/day intramuscularly (n = 7), and rats treated with cyclosporine at a dose of 10 mg/kg/day intramuscularly (n = 7). Grafts were removed on day 71 in the treated groups and on rejection in the control group. We blindly scored graft rejection and graft coronary disease on a scale of 0 to 4. Graft-infiltrating lymphocytes were investigated by flow-cytometric analysis with the following monoclonal antibodies: W3/25, anti-helper T lymphocyte; OX8, antisuppressor and cytotoxic T lymphocyte; and OX39, antiinterleukin-2 receptor. No difference of graft rejection was found between the two treated groups (FK506 1.66 +/- 0.49 versus cyclosporine 1.45 +/- 0.37), but the FK506 group showed severe graft coronary disease (FK506 2.14 +/- 0.82 versus cyclosporine 0.78 +/- 0.17; p less than 0.01) in this model. In flow-cytometric analysis, we found an increased proportion of OX8-positive lymphocytes (FK506 25.7 +/- 6.4 versus cyclosporine 4.9 +/- 2.4, p less than 0.01). These results suggest that suppression of cytotoxic T lymphocytes may be involved in graft coronary disease.
Arai
S
S
2nd Department of Surgery, Okayama University Medical School, Japan.
Teramoto
S
S
Senoo
Y
Y
D000818:Animals; D003327:Coronary Disease / Q000276:immunology* / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus