Is IL-17 causally involved in the proinflammatory role of the sympathetic nervous system?

Abstract

The proinflammatory cytokine Interleukin 17 (IL-17) is considered an important mediator of inflammation in several autoimmune diseases. It is secreted by immune cells such as Th17 cells, and its receptors are ubiquitously expressed. Recently we observed in the model of murine antigen-induced arthritis (AIA) that the anti-inflammatory and the anti-nociceptive effect of sympathectomy was accompanied by a significant reduction of Th17 responses (Ebbinghaus et al., Ann Rheum Dis 2012;71:253–261). This raised the question whether IL-17 is a major player in neuro-immune interactions in murine AIA. In order to further elucidate the role of IL-17 in AIA and in the proinflammatory effect of the sympathetic nervous system, we performed several experiments in AIA using IL-17 knockout mice, a neutralizing anti-IL-17-antibody and adrenoceptor agonists. We found that destruction of sympathetic neurons (by chemical sympathectomy) in the absence of IL-17 still acts anti-inflammatory in AIA. Furthermore neutralization of IL-17 in wild-type C57Bl/6 mice did not effectively reduce joint swelling but significantly reduced secondary mechanical hyperalgesia and attenuated gait abnormalities of the ipsilateral hind limb in the acute stage of inflammation. In addition treatment of AIA-derived lymphocytes ex vivo with α- or β-adrenoceptor agonists did not change their ability to produce IL-17 following re-stimulation with the antigen. Taken together we found that IL-17 alone is not the major player in AIA. Furthermore we did not obtain evidence that IL-17 is causally involved in the proinflammatory effect of the sympathetic nervous system. Nonetheless we found a robust involvement of IL-17 in inflammation-evoked mechanical hyperalgesia.