IMMUNOSUPPRESSIVE DOSE OF AZATHIOPRINE INHIBITS REPLICATION OF HUMAN CYTOMEGALOVIRUS INVITRO

Azathioprine (Aza) was found to have anti-human cytomegalovirus (HCMV) activity in vitro at concentrations used for immunosuppression therapy. The dose of Aza for 50% plaque reduction was 0.592-mu-g/ml for HCMV in human embryonic lung (HEL) cells, but those of Aza for 50% plaque reduction for herpes simplex virus (HSV) and varicella-zoster virus were more than 20-mu-g/ml. The dose of Aza for 50% reduction of the HCMV yield in infected cells was 0.25-mu-g/ml, while that for 50% reduction of the HSV yield in infected cells was more than 50-mu-g/ml. The dose of Aza for 50% growth inhibition of HEL cells was 30-mu-g/ml, and 50.7 and 120 times greater than the doses for 50% reduction of the plaque formation and the yield of HCMV, respectively. Thus Aza was found to have a strong anti-HCMV activity at concentrations used for immunosuppression. When HCMV infected cells were treated with cyclosporine (CsA: 0.2-mu-g/ml) and prednisolone (Pred: 0.3-mu-g/ml) simultaneously with Aza, the doses of Aza for 50% reduction of plaque formation and the yield of HCMV were 0.73 and 0.32-mu-g/ml, respectively. Thus an inhibitory effect of Aza was also observed in HCMV-infected cells treated with CsA and Pred at their concentrations used for immunosuppression. Maintenance of an anti-HCMV dose of Aza in combination with CsA and Pred might establish not only satisfactory immunosuppression but also suppression of HCMV infection in transplant recipients.