The Effect of Etanercept on the Human Cutaneous Allergic Response

Abstract

RATIONALE: TNF-alpha, derived from mast cells and other sources, induces a variety of inflammatory events. We therefore examined the effect of TNF-alpha inhibition in a human cutaneous allergen challenge model.METHODS: Intradermal skin testing with standardized dust mite allergen was performed on sensitive subjects with perennial allergic rhinitis. The acute phase response (APR) was measured at 15 minutes. Wheal size and skin biopsies were taken at 2 hours and again at 16 hours (the late phase response (LPR)). Subjects then received open-label etanercept, a soluble TNF-alpha receptor inhibitor, 50 mg subcutaneously every three days for a total of 3 doses. Intradermal skin testing and biopsies were repeated 24 hours after the last etanercept dose.RESULTS: So far, 6 subjects have completed the study. Following administration of etanercept, APR size was reduced in 4 of 6 subjects by a mean of 22%. Two of the subjects did not have a LPR. In 3 of the 4 subjects who developed an LPR, etanercept reduced the LPR by a mean of 59%. To date, levels of tissue eosinophils, and endothelial staining for E-selectin and VCAM-1, counted blindly, do not appear to correlate with reductions in either the APR or LPR. No adverse events were noted in response to anti-TNF therapy.CONCLUSIONS: Anti-TNF therapy appears to inhibit both the APR and LPR macroscopic responses in this intradermal allergen challenge model. This inhibition may be independent of endothelial activation and eosinophil recruitment. RATIONALE: TNF-alpha, derived from mast cells and other sources, induces a variety of inflammatory events. We therefore examined the effect of TNF-alpha inhibition in a human cutaneous allergen challenge model. METHODS: Intradermal skin testing with standardized dust mite allergen was performed on sensitive subjects with perennial allergic rhinitis. The acute phase response (APR) was measured at 15 minutes. Wheal size and skin biopsies were taken at 2 hours and again at 16 hours (the late phase response (LPR)). Subjects then received open-label etanercept, a soluble TNF-alpha receptor inhibitor, 50 mg subcutaneously every three days for a total of 3 doses. Intradermal skin testing and biopsies were repeated 24 hours after the last etanercept dose. RESULTS: So far, 6 subjects have completed the study. Following administration of etanercept, APR size was reduced in 4 of 6 subjects by a mean of 22%. Two of the subjects did not have a LPR. In 3 of the 4 subjects who developed an LPR, etanercept reduced the LPR by a mean of 59%. To date, levels of tissue eosinophils, and endothelial staining for E-selectin and VCAM-1, counted blindly, do not appear to correlate with reductions in either the APR or LPR. No adverse events were noted in response to anti-TNF therapy. CONCLUSIONS: Anti-TNF therapy appears to inhibit both the APR and LPR macroscopic responses in this intradermal allergen challenge model. This inhibition may be independent of endothelial activation and eosinophil recruitment.