Enhancement of the effect of low-dose cyclosporin A by sulphasalazine in prevention of cardiac allograft rejection in the rat.
Sulphasalazine (SASP) is an immunomodulatory compound with disease-modifying activity in ulcerative colitis and in other autoimmune disorders. SASP was previously shown to prolong the survival of heart allografts in rats treated with cyclosporin A (CyA) for 9 days after transplantation. We have now evaluated whether SASP also exerts a beneficial effect under continuous treatment with CyA, when CyA is discontinued after 14 days, or alone if given 10 days prior to transplantation. Cardiac grafts were transplanted from PVG donors to Wistar/Kyoto recipients using an accessory cervical heart transplantation technique. Rejection was defined as the absence of palpable contractions and occurred in the control group in a very reproducible manner on day 8 or 9. SASP alone was given orally (100 mg/kg body weight) starting 10 days before transplantation and resulted in a minor prolongation of graft survival. When SASP was given in addition to oral CyA (1 mg/kg or 2 mg/kg from day 0 to rejection) there was a significant prolongation in graft survival [from medians of 8 (range 6-11) and 9 (range 8-11) days, respectively, to medians of 10 (range 8-15) and 12 (range 11-15) days, respectively]. When SASP was given from day 0 to rejection, in addition to a schedule of oral CyA (10 mg/kg) for 15 days, there was no prolongation of graft survival [median of 30 (range 26-42) days vs median of 32 (26-38) days]. The data show that SASP acts as a weak immunosuppressive agent which enhances the effect of CyA given at a low dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, University of Uppsala, Sweden.
A
A
Wanders
G
G
Tufveson
B
B
Gerdin
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006084:Graft Rejection / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012460:Sulfasalazine / Q000008:administration & dosage*; D014184:Transplantation, Homologous
D012460:Sulfasalazine; D016572:Cyclosporine