J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1077/09 $2.00
Volume 186, Number 7, October 6, 1997 1077-1085

The  Chemokine, Interleukin 8, Inhibits the Antiviral Action of Interferon  

By Khalid S.A. Khabar,^* Fahad Al-Zoghaibi,^* Mohammed N. Al-Ahdal,^* Tsugiya Murayama, Mohammed Dhalla,^* Naofumi Mukaida,^§ Mohammed Taha,^* Sultan T. Al-Sedairy,^* Yunus Siddiqui,^* George Kessie,^* and Kouji Matsushima

From the ^* Department of Biological and Medical Research, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia 11211;  Department of Microbiology, Kanazawa Medical University, Ishikawa 920-0; ^§ Department of Pharmacology, Kanazwa University, Kanazawa 920; and  Department of Molecular Preventive Medicine, University of Tokyo, Tokyo 113, Japan

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- 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- antiviral activity was associated with reduced 2,5-A oligoadenylate synthetase activity, a pathway well correlative with the anti- encephalomyocarditis virus action of IFN-. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.

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