The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1997/10/1077/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 7, October 6, 1997 1077-1085

Articles

The {alpha} Chemokine, Interleukin 8, Inhibits the Antiviral Action of Interferon {alpha}

Khalid S.A. Khabar*, Fahad Al-Zoghaibi*, Mohammed N. Al-Ahdal*, Tsugiya Murayama{ddagger}, 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; {ddagger} 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-{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.

Address correspondence to Dr. Khalid S.A. Khabar, Head, Interferon and Cytokine Research Unit, Department of Biological and Medical Research, MBC-03, King Faisal Specialist Hospital and Research Center, PO Box 3354; Riyadh 11211, Saudi Arabia. Phone: 966-1-442-7878; FAX: 966-1-442-7858; E-mail: khabar{at}kfshrc.edu.sa

1 Abbreviations used in this paper: CMV, cytomegalovirus; CPE, cytopathic effects; EMCV, encephalomyocarditis virus; FBS, fetal bovine serum; LU, laboratory units; mRNA, messenger RNA; MTS, tetrazolium salt; OAS, 2',5'-oligoadenylate synthetase; RIPA, radioimmunoprecipitation; RT, reverse transcriptase; VSV, vesicular stomatitis virus.

Part of this work was presented at the first joint meeting of the International Cytokine Society (ICS) and International Society for Interferon and Cytokine Research (ISICR), Geneva, Switzerland, October 1996.


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