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Khabar, K.S. et al.

Khabar, Al-Zoghaibi, Al-Ahdal, Murayama, Dhalla, Mukaida, Taha, Al-Sedairy, Siddiqui, Kessie, Matsushima,

The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha.

Interferon ( IFN) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. Like IFN, the proinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopathic effect assay for IFN, we found that IL-8 can inhibit IFN-alpha activity in a dose-dependent manner. This action was reversed by specific monoclonal antibodies to IL-8. The chemokine was able to attenuate the IFN-mediated inhibition of viral replication as determined by measuring infectious virus yield. IL-8 also diminished the ability of IFN to inhibit an early stage of viral replication since IL-8 attenuated the inhibition of the formation of viral proteins. It appeared that IL-8 interfered with a late rather than an early step of IFN-mediated pathway such as early gene expression. The IL-8 inhibitory action on IFN-alpha antiviral activity was associated with reduced 2',5'-A oligoadenylate synthetase activity, a pathway well correlative with the anti- encephalomyocarditis virus action of IFN-alpha. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.[1]

References

The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha. Khabar, K.S., Al-Zoghaibi, F., Al-Ahdal, M.N., Murayama, T., Dhalla, M., Mukaida, N., Taha, M., Al-Sedairy, S.T., Siddiqui, Y., Kessie, G., Matsushima, K. J. Exp. Med. (1997) [Pubmed]

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