Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts

Masahiro Oka, Carola Berking, Mark Nesbit, Kapaettu Satyamoorthy, Helmut Schaider, George Murphy, Masamitsu Ichihashi, Edward Sauter, Meenhard Herlyn

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    Abstract

    Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL- 8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.

    Original languageEnglish
    Pages (from-to)595-604
    Number of pages10
    JournalLaboratory Investigation
    Volume80
    Issue number4
    Publication statusPublished - 04-2000

    All Science Journal Classification (ASJC) codes

    • Pathology and Forensic Medicine

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  • Cite this

    Oka, M., Berking, C., Nesbit, M., Satyamoorthy, K., Schaider, H., Murphy, G., Ichihashi, M., Sauter, E., & Herlyn, M. (2000). Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. Laboratory Investigation, 80(4), 595-604.