Cantharidin-induced inflammation in mouse ear model for translational research of novel anti-inflammatories.
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.
GSK Research Centre Zagreb Ltd., Zagreb, Croatia. Vanesa.IveticTkalcevic@glpg.com
Vanesa
V
Ivetic Tkalcevic
Boska
B
Hrvacic
Martina
M
Bosnar
Snjezana
S
Cuzic
Berislav
B
Bosnjak
Vesna
V
Erakovic Haber
Ines
I
Glojnaric
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D002193:Cantharidin / Q000008:administration & dosage / Q000633:toxicity*; D017291:Clarithromycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010032:Otitis Externa / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D057170:Translational Research, Biomedical / Q000379:methods
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D007509:Irritants; D017963:Azithromycin; D017291:Clarithromycin; D002193:Cantharidin