Auricular Chondritis Caused by Metal Ear Tagging in C57BL/6 Mice

Abstract

Abstract. Although it has been shown that auricular chondritis in rats is caused by the use of metal identification ear tags, the pathogenesis remains unclear. Based on the hypothesis that the auricular chondritis is caused by metal ions released from metal identification ear tags, we investigated the pathogenesis in male C57BL/6 mice tagged with metal identification ear tags. Twenty-six weeks after the attachment of the ear tags, visible increases in the thickness of the auricle were observed, and the concentrations of copper and iron in the tagged ears were significantly increased (P , .05) in the tagged ears compared with the untagged ears. There was up-regulation of metallothionein (MT)-I and MT-II mRNA in the tagged ears, and this was confirmed by immunohistologic staining of the destroyed cartilage. Histopathologically, there were observed severe chondritis with extensive granulomatous inflammation, newly formed cartilage nodules, and osseous metaplasia accompanied by cellular infiltrates, such as CD4 T lymphocyte, macrophages, neutrophils, and mast cells, and expression of Th1 cytokines, such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 in the tagged ear. Based on these results, we concluded that the release of copper and iron ions from the metal ear tags played a major role in the onset of auricular chondritis. Subsequent cellular interactions, such as CD4 T cells, macrophages, fibroblasts, and mast cells, mediated by cytokines, such as tumor necrosis factoralpha and interferon-gamma, caused an autoimmune response that may have led to the progression of auricular chondritis as an autoimmune disease.

Malignant Pilomatricoma in 3 Dogs

“…Basal cell carcinomas were labeled by cytokeratins 5, 6, 8, 14, and 18. 32 In other studies, 16,30 basaloid and maturing cells (but not ghost cells) of malignant pilomatricoma variably reacted with antibodies to cytokeratin 8. Cytokeratin 5 antibodies variably labeled malignant pilomatricoma basaloid cells, ghost cells, and squamoid areas, with numerous nonreactive areas.…”

Mouse

“…Inflammatory changes in the skin may also be secondary to the presence of mites or immune complex-mediated vasculitis (Andrews et al 1994, Frith & Ward 1988. Similar degenerative and inflammatory changes in the ears have been associated with excessive grooming or the presence of metal ear tags (Bell et al 1970, Kitagaki & Hirota 2007.…”

Auricular chondrosis in a horse

“…The treatment is often surgical, with the use of multiple antibiotic combinations. Chondritis has been associated with metal ear tags in mice whereby release of copper and iron ions played a major role in the onset by inducing an autoimmune response 5 …”

“…Auricular chondritis, which is an inflammatory disease of connective tissue characterised by the destruction of hyaline and elastic cartilages, is recognised in laboratory rats, 1,2 mice, 3–5 cats, 6–8 dogs 8 and humans 9–11 . The aetiology is unknown, but autoimmune disease is suspected because anti‐cartilage antibodies have been demonstrated in the sera of humans with this disease 1 .…”