Tetrandrine potently inhibits herpes simplex virus type-1-induced keratitis in BALB/c mice

This study investigated the effect of tetrandrine (TDR) on ex-perimental herpes simplex keratitis (HSK) in mice. BALB/c mice were di-vided as follows: Group I, untreated; Group 2, acyclovir (ACV)-treated from day o postinfection; Group 3, ACV-treated from day 7; Group 4, TDR-treated from day O; and Group 5, TDR-treated from day 7. All mice were infected in the right cornea with herpes simplex virus (HSV) type I. TDR 30 mg/kg and ACV 120 mg/kg were administered intraperitoneally daily. The mice were observed for 14 days postinfection. Clinical inflammatory reactions and ocular histopathology were analyzed. The herpes specific antibody response and the delayed type hypersensitivity (DTH) response were stud-ied. Of the 22 untreated mice, 16 developed HSK (incidence, 72.7%). TDR given from day 7 reduced the HSK incidence to 8.5% (p< 0.01); the inci-dence of HSK was 45.4% in mice treated with TDR from day o (p >0.05). Systemic ACV given from day o inhibited HSK development (P<0.01); ACV given from day 7 resulted in an HSK incidence of 50% (p >0.05). The specific anti-HSV antibody response in the serum of mice treated with TDR or ACV either from day o or day 7 was significantly less than that of un-treated mice (p<0.01 and p<0.05, respectively), and TDR treatment sup-pressed DTH responses to HSV (p<0.05). Systemic TDR administered after HSV inoculation of the cornea significantly modulates murine HSK devel-opment at least partly by modifying the host immune/inflammatory response to the virus.