Immunosuppressive dose of azathioprine inhibits replication of human cytomegalovirus in vitro.
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 micrograms 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 micrograms/ml. The dose of Aza for 50% reduction of the HCMV yield in infected cells was 0.25 micrograms/ml, while that for 50% reduction of the HSV yield in infected cells was more than 50 micrograms/ml. The dose of Aza for 50% growth inhibition of HEL cells was 30 micrograms/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 microgram/ml) and prednisolone (Pred: 0.3 microgram/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 micrograms/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.
Shiraki
K
K
Department of Virology, Osaka University School of Medicine, Osaka, Japan.
Ishibashi
M
M
Okuno
T
T
Namazue
J
J
Yamanishi
K
K
Sonoda
T
T
Takahashi
M
M
D000998:Antiviral Agents; D001379:Azathioprine / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011239:Prednisolone / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D003524:Cyclosporins; D011239:Prednisolone; D001379:Azathioprine