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Br J Clin Pharmacol ; 72(6): 912-20, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21595743

ABSTRACT

AIM: Pharmacological profiling techniques, such as the cantharidin-induced skin blister, may be used to assess the anti-inflammatory properties of novel drugs. However, no data are available on the reproducibility of this technique or on the blocking effect of anti-inflammatory drugs, such as anti-TNF and corticosteroids. METHODS: A group of 30 healthy subjects were randomized into three parallel groups treated with placebo, oral methylprednisolone 20 mg day(-1) for 7 days or anti-tumour necrosis factor (TNF) (adalimumab, Humira®, Abbott) 40 mg s.c. single dose. A first blister was induced at baseline and collected, immediately before the start of treatment and a second blister was obtained 7 days after the start of treatment. The total number of cells, the cell viability and the differential cell count were evaluated by two independent observers, who were blind to treatment. anova was used to compare change from baseline among the three groups before pairwise comparisons. RESULTS: Among the placebo group, there was no significant difference in the total cell count, neutrophils, eosinophils and monocytes between day 1 and day 7. Methylprednisolone inhibited the eosinophil influx in mean % (95% CI) (-1.0 (-1.7, -0.3); P < 0.02) and absolute (P < 0.02) values, while anti-TNF inhibited the neutrophil influx in mean % (95% CI) (-19.3 (-29.5, -9.1); P < 0.01) and absolute (P < 0.05) values. CONCLUSIONS: The cantharidin-induced skin blister is a safe, well tolerated and reproducible procedure. Pre-treatment with anti-TNF or methylprednisolone inhibited the neutrophilic or eosinophilic trafficking, respectively. It could be useful in profiling anti-inflammatory drugs regarding their effects on the cellular inflammatory response.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Blister/chemically induced , Cantharidin/toxicity , Inflammation/chemically induced , Adalimumab , Adult , Antibodies, Monoclonal, Humanized/pharmacology , Blister/drug therapy , Blister/pathology , Eosinophils/drug effects , Eosinophils/metabolism , Female , Humans , Inflammation/drug therapy , Inflammation/pathology , Irritants/toxicity , Male , Methylprednisolone/pharmacology , Models, Biological , Neutrophils/drug effects , Neutrophils/metabolism , Reproducibility of Results , Skin/pathology , Tumor Necrosis Factor-alpha/antagonists & inhibitors
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