In Vitro and Systemic Effects of Recombinant Bovine Interferons on Natural Cell-Mediated Cytotoxicity in Healthy and Bovine Herpesvirus-1-Infected Cattle

Abstract

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 herpesvirus-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-γ caused a transient rise in NC activity, which was both dose and route dependent. Treatment of calves with IFN-α, or IFN-γ 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.