Abrogation of Junin virus encephalitis by critical cyclophosphamide timing and dosage

Junin virus-induced encephalitis in suckling mouse is a delayed-type hypersensitivity reaction, whose immunopathologic nature has been proven by suppressing the thymus-dependent response. Cyclophosphamide (CY) given at day +6 post-infection (p.i.) has been shown to modulate infection, presumably by TDTH lymphocyte inactivation. To determine critical timing and i.p. drug dose, brain histology and survival were studied in 3-day-old Balb/c mice, inoculated i.c. with Junin virus. Optimal protection was achieved with a non-toxic, 50 mg/kg CY dose at day 6 p.i. (+6): no brain tissue damage was detected in animals killed at day +12, when the necropsied controls exhibited widespread lesions. Other timings (day +3, +4, +5) proved less effective. As regards alternative dosage at day +6, 30 mg was useless, and severe leptomeningitis was evident, whereas 40 mg significantly lowered mortality, and lesions were much milder and less constant. It seems that the 50 mg/kg CY dose must be administered at a critical time p.i. to inactivate sensitized TDTH lymphocytes and to reduce mortality and CNS pathology significantly.