Article
IL-17A does not contribute to the impact of the sympathectic nervous system on experimental arthritis
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Authors
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Matthias Ebbinghaus
- Universitätsklinikum Jena, Institut für Physiologie I, Jena
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Susanne Hensellek
- Universitätsklinikum Jena, Institut für Physiologie I, Jena
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Firas Subhi Salah
- Universitätsklinikium Jena, Institut für Physiologie I, Jena
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Rolf Bräuer
- Universitätsklinikum Jena, Institut für Pathologie, Jena
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Hans-Georg Schaible
- Universitätsklinikum Jena, Institut für Physiologie I, Jena
| Published: | September 1, 2015 |
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Outline
Text
Introduction: Interleukin 17 (IL-17), a current target for the therapy of several inflammatory diseases, is also assumed to be a mediator of inflammation in experimental models of arthritis. In murine antigen-induced arthritis (AIA) a strong anti-inflammatory effect was achieved by systemic sympathectomy in C57BL/6J mice. This effect was accompanied by a significant reduction of Th17 responses. In addition, lymphocytes produce less IL-17 after antagonistic beta-adrenergic treatment in vitro. This raised the question whether IL-17 is causally involved in the proinflammatory role of the sympathetic nervous system in AIA.
Methods: Monoarticular antigen-induced arthritis (AIA) was induced in preimmunized C57BL/6J mice and in IL-17-/- mice [1]. Chemical sympathectomy with 6-hydroxydopamine was carried out before AIA elicitation (day -1). In the course of AIA the severity of inflammation (joint swelling, histopathology) was monitored and the release of cytokines and calcitonin gene-related peptide (CGRP) in different tissues was determined by ELISA. In acute AIA the number of splenic T helper cells was determined by FACS analysis. Additionally IL-17-/- mice were checked for the expression of IL-17 subtypes by PCR.
Results: First we found that IL-17-/- mice express all subtypes of IL-17 (B, C, D, E, F) except subtype “A”. In AIA IL-17-/- mice showed severe signs of inflammation similar as wild type mice, and sympathectomy in the absence of IL-17A still acted anti-inflammatory. Furthermore, in IL-17-/- mice, significantly less IL-2, IL-6 and IFNγ was measured at the inflamed joint after sympathectomy and the number of splenic T helper 1 and T regulatory cells in IL-17-/- mice was decreased after sympathectomy. But in contrast to wild-type mice, lymphocytes derived from arthritic IL-17-/- mice did not produce less proinflammatory cytokines following previous sympathectomy.
Conclusion: Taken together we found no evidence that IL-17A is essential for sympathetic neuro-immune interactions influencing the severity of AIA. Further studies have to clarify the role of both sympathectomy and IL-17A in the local effects in the joint and in the general immune response.
References
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- Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, Sekikawa K, Asano M, Iwakura Y. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity. 2002 Sep;17(3):375-87.
