Validation of the cantharidin-induced skin blister as an in vivo model of inflammation
Article first published online: 9 NOV 2011
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 72, Issue 6, pages 912–920, December 2011
How to Cite
Dinh, P. H. D., Corraza, F., Mestdagh, K., Kassengera, Z., Doyen, V. and Michel, O. (2011), Validation of the cantharidin-induced skin blister as an in vivo model of inflammation. British Journal of Clinical Pharmacology, 72: 912–920. doi: 10.1111/j.1365-2125.2011.04020.x
- Issue published online: 9 NOV 2011
- Article first published online: 9 NOV 2011
- Accepted manuscript online: 19 MAY 2011 07:30AM EST
- Received; 22 November 2010; Accepted; 13 May 2011; Accepted Article; 19 May 2011
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Techniques to create aseptic inflammatory reactions provide information regarding acute inflammatory pathways and may be used to assess the anti-inflammatory properties of novel drugs.
WHAT THIS STUDY ADDS
• In this study, we have shown that the cantharidin-induced blister is a local inflammatory reaction, safe and well tolerated, with a good intra-subject inter-day reproducibility. This induced blister is inhibited by specific (anti-tumour necrosis factor (TNF)) and non specific (corticosteroids) systemic anti-inflammatory agents. This model could be of interest to evaluate anti-inflammatory agents in their early phase development.
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.