HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Skov, L. Articles by van de Winkel, J. G. J. Search for Related Content PubMed PubMed Citation Articles by Skov, L. Articles by van de Winkel, J. G. J.

IL-8 as Antibody Therapeutic Target in Inflammatory Diseases: Reduction of Clinical Activity in Palmoplantar Pustulosis¹

Lone Skov^*, Frank J. Beurskens, Claus O. C. Zachariae^*, Sakari Reitamo, Jessica Teeling^2,, David Satijn, Kim M. Knudsen^¶, Elmieke P. J. Boot, Debra Hudson, Ole Baadsgaard^¶, Paul W. H. I. Parren^3, and Jan G. J. van de Winkel^,||

^* Department of Dermatology, Copenhagen University Hospital Gentofte, Hellerup, Denmark; Genmab BV, Utrecht, The Netherlands; Department of Dermatology, University of Helsinki, Hospital for Skin and Allergic Diseases, Helsinki, Finland; Medarex, Milpitas, CA 95035; ^¶ Genmab A/S, Copenhagen, Denmark; and ^|| Immunotherapy Laboratory, Department of Immunology, University Medical Center, Utrecht, The Netherlands

IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced clinical disease activity at all five endpoints, which included a 50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose-dependent decreases of IL-8 concentrations immediately following Ab infusion. These data demonstrate a critical role for IL-8 in the pathophysiology of palmoplantar pustulosis. HuMab 10F8 is capable of interrupting IL-8 activity in vivo and represents a candidate for treatment of inflammatory diseases and other pathological conditions associated with IL-8 overproduction.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Genmab A/S and Medarex.

² Current address: Central Nervous System Inflammation Group, University of Southampton, Southampton, U.K.

³ Address correspondence and reprint requests to Dr. Paul W. H. I. Parren, Genmab BV, Yalelaan 60, 3584 CM, Utrecht, The Netherlands. E-mail address: P.Parren{at}genmab.com

⁴ Abbreviations used in this paper: PPP, palmoplantar pustulosis; rhIL-8, recombinant human IL-8; HAHA, human anti-human Ab; MIG, monokine induced by IFN-.