Delay in corneal allograft rejection due to anti-CD4 antibody given alone and in combination with cyclosporin A and leflunomide.
Anti-CD4 monoclonal antibodies (mAbs) have been shown to inhibit in vitro T-cell activation and proliferation to both antigens and mitogens. Animals studies have demonstrated the immunosuppressive potency of anti-CD4 mAbs given in vivo for therapy of autoimmune disease and following allografting. Similarly, leflunomide (LF), a new potent immunosuppressive, has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplant rejection. LF is thought to antagonize cytokine activity, thereby interfering with T-helper-cell-dependent B- and T-lymphocyte proliferation. A new anti-CD4 antibody (RIB 5/2) was investigated alone and in combination with cyclosporin A (CsA) and LF for the treatment of corneal allograft rejection in the rat. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA at 1.5 mg/kg; (3) RIB 5/2 at 2.5 mg/kg; (4) RIB 5/2 at 2.5 mg/kg and CsA at 1.5 mg/kg; (5) RIB 5/2 at 2.5 mg/kg, CsA at 1.5 mg/kg and LF at 10 mg/kg; (6) RIB 5/2 at 4 mg/kg; (7) RIB 5/2 at 4 mg/kg and CsA at 1.5 mg/kg; and (8) RIB 5/2 at 4 mg/kg, CsA at 1.5 mg/kg, and LF at 10 mg/kg. RIB 5/2 was given intraperitoneally at 24 h before surgery, on the day of grafting, and on postoperative day 1 and was continued every 2nd day until the rat had received ten doses in all (postoperative day 15).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015704:CD4 Antigens / Q000276:immunology*; D016039:Corneal Transplantation; D016572:Cyclosporine / Q000008:administration & dosage*; D006084:Graft Rejection / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007555:Isoxazoles / Q000008:administration & dosage*; D000077339:Leflunomide; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013997:Time Factors; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D016572:Cyclosporine; D000077339:Leflunomide