Interleukin-8 Overexpression Is Present in Pyoderma Gangrenosum Ulcers and Leads to Ulcer Formation in Human Skin Xenografts

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...

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Bibliographic Details
Published in:Laboratory investigation 2000-04, Vol.80 (4), p.595-604
Main Authors: Oka, Masahiro, Berking, Carola, Nesbit, Mark, Satyamoorthy, Kapaettu, Schaider, Helmut, Murphy, George, Ichihashi, Masamitsu, Sauter, Edward, Herlyn, Meenhard
Format: Article
Language:English
Subjects:
Adenovirus
Animals
Gene Expression Regulation
Humans
Interleukin-8 - biosynthesis
Interleukin-8 - genetics
Interleukin-8 - immunology
Laboratory Medicine
Medicine
Medicine & Public Health
Mice
Mice, SCID
Pathology
Pyoderma Gangrenosum - etiology
Pyoderma Gangrenosum - immunology
Pyoderma Gangrenosum - pathology
Recombinant Proteins - biosynthesis
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Skin - immunology
Skin - pathology
Skin Transplantation
Transplantation, Heterologous
Ulcer - immunology
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Summary: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.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.3780064