Enhancement of antibody formation against herpes simplex virus in mice by the T-cell mitogen bestatin.

The influence of the T-lymphocyte-stimulating dipeptide bestatin on the induction of neutralizing antibodies against herpes simplex virus type 1 in the mouse was investigated. Dose-response experiments revealed two active ranges from 1 ng/kg to 100 ng/kg and from 10 micrograms/kg to 10 mg/kg or more. Bestatin (10 mg/kg) enhanced antibody levels after primary infection, if injected between day 5 and day 8 after infection with a maximum effect at day 5. Following secondary infections, bestatin was most effective at day 1 after secondary infection. Moreover, the antibody-generating potency of a formalinized herpes simplex virus type 1 vaccine was elevated considerably. Bestatin and silica seemed to be effective systemically. Treatment of mice with silica before virus infection and additionally with bestatin at day 1 after infection resulted in an additive effect on antibody production. Comparable effects could be obtained when polyinosinic acid X polycytidylic acid or indomethacin was combined with bestatin at day 1. It was assumed that certain factors released by macrophages 'sensitize' the antibody-producing system for the enhancing activity of bestatin at day 1. Indeed, culture fluids of macrophages obtained from mice either pretreated with silica or infected by herpes simplex virus were active in enhancing antibody formation upon injection into mice at day 1 in combination with bestatin. Bestatin did not induce interferon activity. No influence of bestatin on the virus content of organs or on mortality was observed.