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The Capital Region of Denmark - a part of Copenhagen University Hospital
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IL-8 as antibody therapeutic target in inflammatory diseases: reduction of clinical activity in palmoplantar pustulosis

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  • 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
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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.

Original languageEnglish
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume181
Issue number1
Pages (from-to)669-79
Number of pages11
ISSN0022-1767
Publication statusPublished - 1 Jul 2008

    Research areas

  • Amino Acid Sequence, Animals, Antibodies, Monoclonal, Cells, Cultured, Epitopes, Humans, Immune Tolerance, Immunotherapy, Inflammation, Interleukin-8, Mice, Mice, Transgenic, Models, Molecular, Molecular Sequence Data, Neutrophils, Protein Binding, Protein Structure, Tertiary, Psoriasis, Time Factors

ID: 45972241