Limb allografts in rats treated with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.
This study examined whether administration of anti-ICAM-1 mAb (monoclonal antibody) and anti-LFA-1 mAb were effective for inhibition of the acute rejection reaction in a rat-limb allograft model. The grafts were carried out using major histocompatibility complex mismatch pairs of rats: ACI rats as the donors and Lewis rats as the recipients. The subjects were of species with completely different major histocompatibility complexes. The average length of survival in this combination was 4.7 +/- 0.6 days. When anti-ICAM-1, anti-LFA-1 mAb, or a combination of both were administered intraperitoneally at 1 mg/kg body weight daily for 7 days after the graft, the mean survival times were 4.3 +/- 0.6, 4.7 +/- 0.6, or 4.7 +/- 0.6 days, respectively. The agents were found to exercise no beneficial effects for transplants. Transplants were then carried out with a single intramuscular administration of FK506 at 3mg/kg body weight on the day of the operation to observe the effect of this adjunct therapy. The mean survival time averaged 16.0 +/- 5.5 days with FK506 alone. Administration of anti-ICAM-1, anti-LFA-1, and both antibodies together with FK506 resulted in mean survival times of 15.4 +/- 3.0, 25.0 +/- 5.8 and 13.2 +/- 5.8 days, respectively. Thus, a significant prolongation of survival time was observed when the combination of anti-LFA-1 mAb and FK506 was used. In contrast, anti-ICAM-1 mAb and FK506 or both mAb and FK506 showed no beneficial effects.
Tsuchida
Y
Y
Department of Orthopedic Surgery, Sapporo Medical University, Japan.
Usui
M
M
Naitoh
T
T
Takahashi
T
T
Murakami
M
M
Uede
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D005121:Extremities / Q000637:transplantation*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D016559:Tacrolimus