title: Neutralization of IL-8 prevents the induction of dermatologic adverse events associated with the inhibition of epidermal growth factor receptor.
abstract: Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance to treatment. Currently, the pathways involved in EGFR inhibitor-induced rash are poorly understood and few treatment options for this adverse event are available. Here, we developed a model for induction of papulopustular rash in healthy human volunteers by subcutaneous injection of the anti-EGFR monoclonal antibody zalutumumab. The injection sites and surrounding skin were evaluated by a dermatologist for the presence or absence of papulopustular rash and skin biopsies were taken to confirm the macroscopical findings by immunohistochemistry. Locally injected zalutumumab induced a papulopustular rash, characterized by acute follicular neutrophil-rich hair follicle inflammation, and thus mimicked adverse events induced by systemic administration of EGFR inhibitors. In this model, we tested the hypothesis that neutrophils, attracted by IL-8, play a central role in the observed rash. Indeed, concomitant local repeat dose treatment with HuMab-10F8, a neutralizing human antibody against IL-8, reduced the rash. Inhibition of IL-8 can therefore ameliorate dermatological adverse events induced by treatment with EGFR inhibitors.
authors: Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark. Nanban01@geh.regionh.dk
authors: Nannie
authors: N
authors: Bangsgaard
authors: Mischa
authors: M
authors: Houtkamp
authors: Danita H
authors: DH
authors: Schuurhuis
authors: Paul W H I
authors: PW
authors: Parren
authors: Ole
authors: O
authors: Baadsgaard
authors: Hans W M
authors: HW
authors: Niessen
authors: Lone
authors: L
authors: Skov
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D007279:Injections, Subcutaneous; D016209:Interleukin-8 / Q000276:immunology*; D009500:Neutralization Tests; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016209:Interleukin-8; C546618:zalutumumab; D066246:ErbB Receptors