Studies on the in vitro biological activities of recombinant bovine tumor necrosis factor (rBoTNF) alpha. I. Synergistic antiviral efficacy of rBoTNF alpha, recombinant bovine interferon gamma (rBoIFN gamma) and their combination.

The recent demonstration of the antiviral activity of recombinant human TNF has launched an interest in the use of TNF alpha for antiviral therapy in veterinary medicine. In the precent report, we demonstrate that pretreatment of bovine cells with rBoTNF alpha reduces the yield of bovine herpesvirus type-1 (BHV-1) from infected cells. Reduction in yield was similar to that observed in the presence of rBoIFN gamma. Similarly, rBoTNF alpha was able to protect bovine cells from virus-induced cytopathology. Enhanced antiviral activity was demonstrated when rBoTNF alpha was administered in combination with rBoIFN gamma. Studies on the induction of 2',5'-oligoadenylate synthetase (2'-5' AS) production by cytokine-treated cells showed that although rBoTNF alpha by itself did not induce 2'-5' AS activity it was capable of enhancing the production of 2'-5' AS by rBoIFN gamma-treated cells. Combination of these two cytokines was also evident in the inhibition of proliferation of treated cells. In contrast, the cytotoxic effect of rBoTNF alpha towards actinomycin D-treated cells was not affected by the combination of rBoTNF alpha with rBoIFN gamma.