Carbocisteine in vivo reduces circulating miR-21 and IL-8 in exacerbated COPD patients

Body: Carbocysteine, reducing exacerbation rate, represents a valid add on therapy in Chronic Obstructive Pulmonary Disease (COPD). The clinical efficacy of carbocysteine is also associated to its anti-oxidant and anti-inflammatory activities. Assessment of microRNAs and pro-inflammatory cytokines in sera could be an approach to evaluate disease activity and severity. MiR-21 expression and IL-8 levels are both increased in COPD. Cigarette smoke extract (CSE) increases the miR-21 and IL-8 in human bronchial epithelial (16HBE) cells. Limited information are available on the in vivo effects of carbocysteine on systemic inflammatory markers. Aims: The aim of this study is to assess, in vivo, whether carbocysteine, can affect inflammatory markers MiR-21, IL-8 as well as functional parameters in COPD patients evaluated at the onset and at the end of an exacerbation. Methods: No smokers, Smokers, stable and exacerbated COPD patients were recruited. All exacerbated COPD patients received add on therapy with corticosteroids and antibiotics with or without carbocysteine for 20 days. Clinical and functional assessment and blood sample collection were performed at the onset and at the end of the exacerbation. Circulating miR-21 and IL8 were evaluated by Real Time PCR and by ELISA, respectively. Results: Smokers, stable and exacerbated COPD showed high levels of circulating miR-21 and IL8 . The addition of carbocysteine in exacerbated patients improves FEV1 and FEF25-75 and reduced circulating miR-21 and IL8 release. Conclusions: The present study provides compelling evidences that carbocysteine may reduce exacerbation rate in COPD patients downregulating some parameters of systemic inflammation.