| Abstract: |
Cancer patients receiving epidermal growth factor receptor (EGFR) antibody therapy often experience an acneiform rash of uncertain etiology in skin regions rich in pilosebaceous units. Currently, this condition is treated symptomatically with very limited, often anecdotal success. Here, we show that a monoclonal antibody targeting murine EGFR, ME1, caused a neutrophil-rich hair follicle inflammation in mice, similar to that reported in patients. This effect was preceded by the appearance of lipid-filled hair follicle distensions adjacent to enlarged sebaceous glands. The cytokine tumor necrosis factor-α (TNFα), localized immunohistochemically to this affected region of the pilosebaceous unit, was specifically upregulated by ME1 in skin but not in other tissues examined. Moreover, skin inflammation was reduced by cotreatment with the TNFα signaling inhibitor,etanercept, indicating the involvement of TNFα in this inflammatory process. Interleukin-1, a cytokine that frequently acts in concert with TNFα, is also involved in this process given the efficacy of the interleukin-1 antagonist Kineret. Our results provide a mechanistic framework to develop evidence-based trials for EGFR antibody-induced skin rash in patients with cancer. ©2009 American Association for Cancer Research. |
| Keywords: |
immunohistochemistry; controlled study; unclassified drug; nonhuman; mouse; animals; mice; animal tissue; animal experiment; animal model; receptor, epidermal growth factor; mice, scid; cetuximab; skin; antibodies, monoclonal; immune response; tumor necrosis factor alpha; neutrophil; tumor necrosis factor-alpha; immunoglobulin g; reverse transcriptase polymerase chain reaction; anti-inflammatory agents, non-steroidal; etanercept; dermatitis; enzyme-linked immunosorbent assay; disease models, animal; epidermal growth factor receptor antibody; exanthema; interleukin 1; monoclonal antibody me1; recombinant interleukin 1 receptor blocking agent; hair follicle inflammation; sebaceous gland; skin inflammation; interleukin 1 receptor antagonist protein; interleukin-1; receptors, tumor necrosis factor
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