[Rescue effect of 15-deoxyspergualin for acute rejection on heart transplantation--using a rat model].
15-Deoxyspergualin (DSG) attracts a lot of attention as an immunosuppressive drug which has less side effects these days. In the present study, we researched the rescue effect of DSG for acute rejection on heart transplantation (HTX) by using rat models. We performed 40 heterotopic heart transplantation models. We injected them DSG (group A: 5 mg/kg/day, group B: 10 mg/kg/day) intravenously through 3 days, starting from the 3rd day the 4th day, and the 5th day after HTX. Our previous study showed the pathology on the 3rd day after HTX corresponded to mild rejection, the 4th day to moderate rejection, and the 5th day to severe rejection. One day after the injection was completed, the recipients were sacrificed. The rescue effect was histopathologically assessed by H-E stain, and the action mechanism of DSG was considered by immunohistochemical stain using monoclonal antibodies, which were against CD4 positive cells, CD8 positive cells, and macrophages. In result, the rescue effect of DSG was significant in all groups, in comparison with controls, which had no immunosuppression. And the rescue effect of group B was superior to group A. We also found using a immunohistochemical technique, that DSG inhibited the accumulation of CD4 and CD8 positive cells. We concluded the rescue effect of DSG for acute rejection on HTX was significant, especially in 10 mg/kg/day even in the severe rejection. And the suppression of helper and cytotoxic T cells accumulation might be one of the action mechanisms of DSG.
Bonkohara
Y
Y
Department of Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical College.
Hachida
M
M
Nonoyama
M
M
Hoshi
H
H
Imamaki
M
M
Saito
S
S
Koyanagi
H
H
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000188:drug therapy*; D006146:Guanidines / Q000627:therapeutic use*; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus