Anti IL-17A therapy inhibits bone loss in TNF-α-mediated murine arthritis by modulation of the T-cell balance
✍ Scribed by Karin Zwerina; Marije Koenders; Axel Hueber; Renoud J. Marijnissen; Wolfgang Baum; Gisela Ruiz Heiland; Mario Zaiss; Iain Mclnnes; Leo Joosten; Wim van den Berg; Jochen Zwerina; Georg Schett
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 499 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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.