In vitro and systemic effects of recombinant bovine interferons on natural cell-mediated cytotoxicity in healthy and bovine herpesvirus-1-infected cattle.

There is now evidence to suggest that the beneficial effect of treatment of calves with recombinant bovine interferons (IFNs) on the outcome of an infection with bovine herpes-virus-1 (BHV-1) may in part be due to effects other than its direct antiviral activity. This evidence prompted us to study the effect of IFNs on natural cell-mediated cytotoxicity (NC) as a possible mechanism in curtailing clinical disease. In vitro treatment of blood leukocytes not only augmented cytotoxicity to NC-susceptible target cells, but also to cell types usually resistant to killing. In vivo treatment of healthy cattle with IFN-gamma caused a transient rise in NC activity, which was both dose and route dependent. Treatment of calves with IFN-alpha 1 or IFN-gamma prior to BHV-1 infection prevented or diminished the suppression of NC activity usually seen following virus infection. The effect could neither be correlated with serum IFN titers nor with conventional hematologic parameters. A possible mechanism for the IFN effect involving the ontogeny of bovine NC-effector cells and the biological consequences for the local antiviral defense in the lung are discussed.