Cardiac allografts in rat recipients with simultaneous use of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies leads to accelerated graft loss.

Cardiac allografts from Fisher rats underwent acute rejection in Wistar King Aptekman/Hokkaido (WKAH) recipient rats. ICAM-1 molecule was induced in grafted myocytes and interstitial cells during the rejection. LFA-1 (+) inflammatory cells heavily infiltrated into rejected allografts. Monoclonal antibodies to rat ICAM-1 or LFA-1 were administered intravenously to WKAH rats receiving Fisher cardiac allografts for 3-7 consecutive days after transplantation. Anti-LFA-1 treatment for 7 consecutive days prolonged allograft survival, and two of these obtained a long-term survival. While 2 out of 13 allografts survived more than 100 days in the anti-ICAM-1-treated groups, anti-ICAM-1 treatment did not affect allograft survival in the other recipients. Surprisingly, simultaneous use of both anti-ICAM-1 and anti-LFA-1 antibodies resulted in accelerated graft loss with interstitial edema, diffuse myocardial degeneration, vascular injury and scattered hemorrhage. Thus, beneficial effects on allograft survival were partially seen when recipients were given anti-ICAM-1 or anti-LFA-1 antibody alone. However, serious disadvantage in preventing rejection was clearly seen when both anti-ICAM-1 and anti-LFA-1 antibodies were used together.