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PLoS By Category | Recent
PLoS Articles
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Dermatology - Immunology - Oncology - Pharmacology
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Neutralization of IL-8 Prevents the Induction of Dermatologic Adverse Events Associated with the Inhibition of Epidermal Growth Factor Receptor
Published:
Monday, June 25, 2012
Author:
Nannie Bangsgaard et al.
by Nannie Bangsgaard, Mischa Houtkamp, Danita H. Schuurhuis, Paul W. H. I. Parren, Ole Baadsgaard, Hans W. M. Niessen, Lone Skov
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.
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