Reovirus type 3 clone 9 increases interleukin-1 alpha level in the brain of neonatal, but not adult, mice

Reovirus Type 3 clone 9 (TSC9)-induced lethal encephalitis is age dependent . We examined the effects of T3C9 inoculated into neonatal and adult mice b y intracerebral, intramuscular, or peroral routes and the effect of lipopol ysaccharide (LPS) on IL-1 alpha levels in the blood and the brain. In paral lel, we measured mice survival to T3C9 challenge, primary replication, and growth in and spread to the brain. The results show that T3C9 infection inc reased IL-1 alpha only in the brain of neonatal mice, whereas LPS enhanced IL-1 alpha in the brain and in the brood in both neonatal and adult mice. I n neonatal mice, a T3C9-induced IL-1 alpha increase coincided with viral re plication-induced nervous tissue injury and preceded death. Anti-IL-1 alpha antibody partially protected neonatal mice against T3C9 peroral challenge, further suggesting that this cytokine is involved in the mechanisms leadin g to lethal encephalitis. In adult mice, T3C9 was not lethal and did not mo dify IL-1 alpha levels although it slowly replicated in nervous tissues whe n inoculated directly into the brain. Together, these results suggest that differences in nervous tissue response to T3C9 replication between newborn and adult mice could account in part for the age-dependent susceptibility t o T3C9-induced lethal encephalitis. (C) 1999 Academic Press.