Role of prostaglandins and non-steroid anti-inflammatory drugs in the pathogenicity of vaccinia virus.

The effect of prostaglandins (PGs) of the A series (A1 and dimethyl PGA2), E1, D2, F2 alpha and PGI2 (prostacyclin) and of inhibitors of PG synthesis (aspirin and indomethacin) on the pathogenicity of vaccinia virus was studied in BALB/c mice. PGs of the A series, D2 and F2 alpha conferred little or no protection to mice against the lethal effects of vaccinia virus. Mice treated with PGE1 showed a dramatic increase in mortality after viral infection. However, when mice were treated with PGI2, their survival was greatly enhanced. Mice treated with aspirin and indomethacin showed a marked increase in mortality. Increased mortality correlated with higher virus yields in target tissues (spleen) and with inhibition of antibody response, whereas the increase in survival correlated with lower virus yields and with normal antibody responses. The significance of our findings is that PGI2 can block the outcome of the disease caused by vaccinia virus whereas other PGs and their inhibitors not only worsen the disease, but may activate and enhance viral infections through immune suppression.