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Eur J Immunol. 2012 Feb;42(2):413-23. doi: 10.1002/eji.201141871. Epub 2011 Dec 20.

Anti IL-17A therapy inhibits bone loss in TNF-α-mediated murine arthritis by modulation of the T-cell balance.

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1
Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.

Abstract

Tumour necrosis factor alpha (TNF-α) is a major inducer for inflammation and bone loss. Here, we investigated whether interleukin (IL)-17 plays a role in TNF-α-mediated inflammation and bone resorption. Human TNF-α transgenic (hTNFtg) mice were treated with a neutralizing anti-IL-17A antibody and assessed for inflammation, cartilage and bone damage. T-cell transcription factors and lymphokine patterns were measured in the LNs. IL-17A inhibition in the absence of IL-1 was also evaluated by treating hTNFtg/IL-1(-/-) mice with an IL-17A neutralizing antibody. IL-17A neutralization had only minor effects on TNF-α-induced inflammation but effectively reduced local and systemic bone loss by blocking osteoclast differentiation in vivo. Effects were based on a shift to bone-protective T-cell responses such as enhanced Th2 differentiation, IL-4 and IL-12 expression and Treg cell numbers. Whereas inflammation in hTNFtg/IL-1(-/-) mice was highly sensitive to IL-17A blockade, no shift in the T-cell lineages and no additional benefit on bone mass were observed in response to IL-17A neutralization. We thus conclude that IL-17A is a key mediator of TNF-α-induced bone loss by closely interacting with IL-1 in blocking bone protective T-cell responses.

PMID:
22101928
DOI:
10.1002/eji.201141871
[Indexed for MEDLINE]
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