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

Zwerina, K. et al. (2011) Anti IL-17A therapy inhibits bone loss in TNF-α-mediated murine arthritis by modulation of the T-cell balance. European Journal of Immunology, 42(2), pp. 413-423. (doi: 10.1002/eji.201141871)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Hueber, Dr Axel
• Authors: Zwerina, K., Koenders, M., Hueber, A., Marijnissen, R.J., Baum, W., Heiland, G.R., Zaiss, M., McInnes, I., Joosten, L., van den Berg, W., Zwerina, J., and Schett, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: European Journal of Immunology
• Journal Abbr.: Eur. J. Immunol.
• ISSN: 0014-2980
• ISSN (Online): 1521-4141
• Published Online: 20 December 2011