Elsevier

Translational Research

Volume 160, Issue 2, August 2012, Pages 137-145
Translational Research

Original Article
Cantharidin-induced inflammation in mouse ear model for translational research of novel anti-inflammatories

https://doi.org/10.1016/j.trsl.2012.02.001Get rights and content

The murine model of cantharidin-induced ear inflammation was profiled in detail for its alignment with the human model and to explore the mechanism of anti-inflammatory activity of the macrolide antibiotics, clarithromycin and azithromycin. Ear swelling in CD1 mice persisted for 7 days, with peak intensity at 16 h after inflammation induction. As in humans, cantharidin (12.5 μg/ear) generated macrophage-inflammatory protein (MIP)-2, monocyte chemoattractant protein (MCP)-1, keratinocyte-derived chemokine (KC), interleukin (IL)-6, IL-1β, and myeloperoxidase (MPO) production, as well as neutrophil accumulation in mouse ear tissue. The tested macrolides, clarithromycin and azithromycin, administered orally (2 × 150 mg/kg) 0.5 h before and 5 h after cantharidin challenge, reduced MIP-2, MCP-1, KC, and MPO concentrations and thereby decreased ear swelling. Our results suggest that cantharidin-induced acute inflammation represents an excellent model for translational research of novel anti-inflammatories.

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Animals

In accordance with previously published reports describing cantharidin-induced ear inflammation, all experiments were performed on male mice. 12, 14, 23, 24 Male CD1 mice, 8- to 10-weeks-old, were obtained from Charles River, France. Animals were kept on wire mesh floors with irradiated maize granulate bedding (Scobis Due, Mucedola s. r. l., Settimo Milanese, Italy) and maintained under standard laboratory conditions (temperature 23–24°C, relative humidity 60% ± 5%, approx. 15 air changes per

Time-course experiment

In an initial experiment, we investigated the time-course of the inflammatory response to topical cantharidin application, determined by ear swelling and histologic analysis of ear tissue (Fig 1).

In contrast to vehicle, topical administration of cantharidin at 25 μg/ear induced ear swelling, measured as an increase in ear weight, by 6 h after administration. Swelling was observable for 168 h (7 days), with peak intensity at 16 h after inflammation induction (Fig 1, A).

Since, for technical

Discussion

Cantharidin blister is well-established model of acute inflammation in humans6, 7 used for monitoring novel treatment strategies.8 Animal models of cantharidin-induced ear edema have been investigated in less detail, ear swelling being the basic experimental output.14, 24 We, therefore, investigated the molecular and cellular mechanisms of inflammation after cantharidin application to the mouse ear to correlate these characteristics with those during cantharidin blister in humans. Histologic

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    This work was supported by GlaxoSmithKline Research Centre Zagreb Ltd.

    Conflict of interest: At the time of study, the authors were all employees of GlaxoSmithKline Research Centre Zagreb Ltd. All authors have read the journal's policy on disclosure of potential conflicts of interest.

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