We quantified these mediators based on our Sirolimus knowledge of previous findings showing that AE improves the immunologic response by increasing levels of Th1 cytokines (Ray and Cohn, 2000) or the anti-inflammatory cytokine IL-10 (Nakagome et al., 2005). However, our results have shown that AE did not modify the expression of either Th1 cytokines (IL-2 and IFN-γ) or IL-10. Altogether, our results may suggest that AE acts directly on Th2 cytokine expression; however, the precise mechanism for such an effect needs to be evaluated in the near future. Levels of exhaled nitric oxide (ENO) have been considered to be a marker of

airway inflammation in asthmatic patients and are increased in asthmatic patients (Prieto et al., 2002). Suman and Beck (2002) suggested that the inhibition of NO synthesis slightly attenuates exercise-induced bronchoconstriction. Although we showed that OVA sensitization increased ENO to levels similar to those observed in another OVA-induced asthma model in guinea pigs (Prado et al., 2005), this increase was not reduced by AE, which suggests that the effect of AE was not mediated by NO in our guinea pig model of asthma. Airway remodeling is an important feature

of the asthmatic airway and seems to be a consequence of non-resolved inflammation as well as an imbalance in the healing and repair process (Irvin and Wenzel, 1995). Airway remodeling is characterized by epithelium desquamation, the increased deposition of

extra-cellular matrix proteins on the airway Lonafarnib concentration wall and airway smooth muscle hypertrophy and hyperplasia (Larché et al., 2003). In our animal model, OVA exposure induced an increase in airway edema and bronchoconstriction as well as in the epithelium and smooth muscle. Although AE reduced airway edema, AE had no effect on airway smooth muscle or on bronchoconstriction. One limitation of our study is that we did not evaluate central (cartilaginous) airways that play an important role in the pulmonary mechanical changes secondary to antigen challenge in asthmatic patients and murine animal see more model of asthma. It is possible that the absence of reduction on airway smooth muscle and bronchoconstriction induced by exercise training may be due the fact that we have evaluated only peripheral and not central airways. In contrast, aerobic training induced a thickening of the airway epithelium. The effect on the airway epithelium observed in our study was previously reported by Chimenti et al. (2007), who demonstrated that aerobic training increases apoptosis and the proliferation rate of the airway epithelium independent of any previous inflammation. Our results have also shown that AE did not reduce OVA-induced airway remodeling in our guinea pig model of asthma, contrary to other mouse studies from our group and others demonstrating the beneficial effects of AE on airway remodeling (Pastva et al., 2004, Vieira et al., 2007 and Silva et al., 2010).