Hydrogen sulphide attenuates lung inflammation caused by resistive breathing

Background & Objectives: During exacerbations of chronic obstructive pulmonary disease (COPD), increased airway inflammation and the accompanying bronchoconstriction lead to significant airway narrowing, i.e. resistive breathing (RB).To isolate the effects of mechanical stressor (i.e. RB) from the accompanying lung inflammation we developed an experimental model of RBthat exhibits both increased inspiratory and expiratory airway resistance, via tracheal banding . Since hydrogen sulphide (H 2 S) plays an important role in vasodilation and inflammation we hypothesized that the administration of a H 2 S fast releasing donor, Na 2 S, will attenuate the lung inflammation. Methods: C57BL/6 mice were studied: 1. Sham operated (controls) 2. Tracheal banded (TB) mice (tracheal surface area restricted to 50% of initial) 3. Sham operated mice treated with injected Na 2 S (10mg/kg) 4. Mice treated with injected Na 2 S 20 min prior to tracheal banding. Results: The proteinexpression of the three H 2 S synthesizing enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3MST), was the same between the TB and sham operated group in the lung. However, the lung mRNA level of CBS was decreased by 57% in TB mice (p=0.009). Finally interleukin IL-6 and IL-1β, were attenuated by 50% (p=0.004)and 45% (p=0.02)in the group of TB mice treated with Na 2 S compared to the TB mice, whereas the expression of TNF-α was the same among the groups. Conclusions: H 2 S ameliorates lung inflammation caused by airway narrowing. Our model of TB might offer new insights by which resistive breathing can enhance inflammation in obstructive lung disease.