IL-8 as antibody therapeutic target in inflammatory diseases: reduction of clinical activity in palmoplantar pustulosis

Lone Skov, Frank J Beurskens, Claus O C Zachariae, Sakari Reitamo, Jessica Teeling, David Satijn, Kim Knudsen, Elmieke P J Boot, Debra Hudson, Ole Baadsgaard, Paul W H I Parren, Jan G J van de Winkel

149 Citationer (Scopus)

Abstract

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 >or=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.

OriginalsprogEngelsk
TidsskriftJournal of immunology (Baltimore, Md. : 1950)
Vol/bind181
Udgave nummer1
Sider (fra-til)669-79
Antal sider11
ISSN0022-1767
StatusUdgivet - 1 jul. 2008

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