Cyclosporin A-induced tolerance is not amplified by the addition of a steroid therapy.
The effect of adding steroids to a cyclosporin A (CyA) schedule designed to induce tolerance to heart allografts in rats was investigated. CyA treatment alone, at a dose of 15 mg/kg per day for 2 weeks, resulted in the successful induction of tolerance (graft survival greater than 100 days) in 70% of the rats. The inclusion of 5 mg/kg of steroids (Solumedrone), administered IM for 40 or 60 days, not only failed to improve this long-term survival (LTS) rate achieved with CyA alone but reduced it from 70% to 50% after 40 days of steroid treatment and to 30% after 60 days of steroid treatment. The administration of 5 mg/kg and 40 mg/kg of steroids during the "high-risk" period for graft rejection (days 30-50 or 40-60) was shown to delay but not prevent subsequent rejections from occurring. Steroid treatment alone (5 mg/kg per day) was found to be ony weakly immunosuppressive. Thus, we have demonstrated that the addition of steroids to a CyA tolerizing schedule was detrimental to the induction of tolerance.
Department of Surgery, Addenbrooke's Hospital, Cambridge, UK.
S M
SM
Lim
K
K
Kogure
D J
DJ
White
D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D051381:Rats; D013256:Steroids / Q000008:administration & dosage*; D013997:Time Factors; D014184:Transplantation, Homologous
D003524:Cyclosporins; D013256:Steroids