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Lamellar leukocyte infiltration and involvement of IL-6 during oligofructose-induced equine laminitis development. - PubMed - NCBI

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Vet Immunol Immunopathol. 2011 Nov 15;144(1-2):120-8. doi: 10.1016/j.vetimm.2011.07.016. Epub 2011 Jul 26.

Lamellar leukocyte infiltration and involvement of IL-6 during oligofructose-induced equine laminitis development.

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The Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton 4343, Australia.


Laminitis is known to involve deregulation of proteases and destruction of the lamellar basement membrane with the host inflammatory response also playing a role. Leukocyte infiltration has been well characterized in the black walnut model of laminitis induction, but not in carbohydrate induced models. Increased gene expression of multiple cytokines, including IL-6, has also been implicated in laminitis development. Using real time PCR, immunohistochemistry and zymography methods, we characterize leukocyte infiltration and IL-6 gene expression in oligofructose (OF) induced laminitis. As well, we use two in vitro models to investigate a role for IL-6 in protease regulation. Laminitis was induced in normal standardbred horses (n=5) by alimentary OF dosing and lamellar biopsies were obtained throughout the 48 h experimental period. Lamellar explants and keratinocytes were also isolated from clinically normal horses for in vitro experiments. We found infiltration of calprotectin-positive leukocytes (monocytes and neutrophils) at 18-24h post oligofructose dosing, while IL-6 gene expression was increased as early as 12h post dosing. Additionally, while we found that IL-6 did not cause significant BM damage in vitro, it did result in increased secreted proMMP-9 levels from lamellar explants. Thus, we find that leukocyte infiltration does occur during oligofructose-induced laminitis development, however, IL-6 gene expression in the lamellae may precede leukocyte infiltration. Additionally, we show IL-6 plays a role in increasing the level of proMMP-9 in vivo in a manner that does not involve keratinocytes.

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