In this study we evaluated the relationship between nitric oxide (NO) and m
acrophage antiviral extrinsic activity. Macrophages activated by intraperit
oneal injection of herpes simplex virus-2 (HSV-2), showed both extrinsic an
tiviral activity and high nitrite production in contrast to nonactivated, r
esident macrophages. The extrinsic antiviral activity was observed in cultu
res of Vero cells infected with HSV-I and HSV-2. The NO inhibitor N-monomet
hyl-L-arginine acetate (L-NMA) impaired the antiviral activity of HSV-elici
ted macrophages. The effect was dose dependent and correlated with a reduct
ion of nitrite in the culture media. The effect of L-NMA was reversed by th
e addition of L-arginine. These data indicate that NO could be responsible
for the described activity. Furthermore, L-NMA treatment resulted in the ag
gravation of HSV-1-induced keratitis in the mouse model, supporting a defen
sive role of NO in the pathogenesis of HSV-1 corneal infection.