Therapeutic activity of deoxyspergualin in comparison with cyclosporin A, and its combined use with cyclosporin A and prednisolone in highly allogeneic skin transplantation in the rat.
The present paper demonstrates the efficacy of a novel immunosuppressive agent, deoxyspergualin (DSG), in rat skin transplantation despite major histocompatible antigen differences, both by itself and in combination with cyclosporin A (CyA) and prednisolone (PD). DSG significantly prolonged the median survival time (MST) of WKAH skin on F344 rats, when given at daily doses of 1.5-12 mg/kg i.p. for 10 days starting from day one after grafting. A significant increase of the MST has been observed also in the rats orally receiving CyA at daily doses of 12.5-50 mg/kg according to the same dosing protocol. DSG was as effective as CyA in prolonging the MST. In contrast, when treatment started 4 days after grafting (at the time of the rejection crisis), DSG (6 mg/kg) was able to reverse the rejection, whereas CyA (50 mg/kg) was not. When DSG (1.5 mg/kg) and CyA (6.25 or 12.5 mg/kg) were given together from day one after grafting, the combined therapy was superior to each monotherapy. Similarly, when DSG (1.5 mg/kg) and PD (10 mg/kg) were given simultaneously from the rejection crisis, the combined therapy was demonstrated to have stronger activity than any of the monotherapies. Moreover, the skin-allografted rats could be switched successfully either from CyA to DSG treatment or from DSG to CyA treatment.
Nemoto
K
K
Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Sugawara
Y
Y
Mae
T
T
Hayashi
M
M
Abe
F
F
Fujii
A
A
Takeuchi
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology*; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D011239:Prednisolone / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D016038:Skin Transplantation / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D006146:Guanidines; D016572:Cyclosporine; D011239:Prednisolone; C037258:gusperimus