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

Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. H owever, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overex pression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressin g the complementary deoxyribonucleic acid encoding human IL-8 (IL-8/Ad5) th at induces a 2000-fold increase in IL-8 expression of infected human fibrob lasts in vitro. Human skin engrafted to severe combined immunodeficiency mi ce and then injected with the recombinant virus demonstrated erythema, an i ntense perivascular infiltration of neutrophils, and extravasation of eryth rocytes after 8 hours. By 12 hours after injection, neutrophils had accumul ated beneath the epidermis, which then necrotized, and one or more ulcers t hat remained for approximately 2 weeks were observed. Clinically and histol ogically, the ulcers resembled pyoderma gangrenosum. These clinical and exp erimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.