THE ALPHA-CHEMOKINE, INTERLEUKIN-8, INHIBITS THE ANTIVIRAL ACTION OF INTERFERON-ALPHA

Interferon (IFN) exhibits a potent antiviral activity in vitro and pla ys a major role in the early defense against viruses. Like IFN, the pr oinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopa thic effect assay for IFN, we found that IL-8 can inhibit IFN-alpha ac tivity in a dose-dependent manner. This action was reversed by specifi c monoclonal antibodies to IL-8. The chemokine was able to attenuate t he IFN-mediated inhibition of viral replication as determined by measu ring infectious virus yield. IL-8 also diminished the ability of IFN t o inhibit an early stage of viral replication since IL-8 attenuated th e inhibition of the formation of viral proteins, It appeared that IL-8 interfered with a late rather than an early step of IFN-mediated path way such as early gene expression. The IL-8 inhibitory action on IFN-a lpha antiviral activity was associated with reduced 2',5'-A oligoadeny late synthetase activity, a pathway well correlative with the anti-enc ephalomyocarditis virus action of IFN-alpha. Understanding pathways th at antagonize IFN action may lead to novel approaches to potentiate en dogenous and therapeutic IFN.