Activin A and follistatin in patients with asthma. Does severity make the difference?

Abstract

Background and objective: Activin A is a pleiotropic cytokine holding a fundamental role in inflammation and tissue remodelling. Follistatin can modulate the bioactivity of activin. We aimed to measure activin A and follistatin in sputum supernatants and bronchoalveolar lavage (BAL) of asthmatic patients and to determine the possible associations with severity as well as with inflammatory and remodelling indices.

Methods: A total of 58 asthmatic patients (33 with severe refractory asthma (SRA)) and 10 healthy controls underwent sputum induction for % cells, activin A, follistatin, eosinophilic cationic protein (ECP), transforming growth factor beta 1 (TGF-β1), IL-13 and IL-8 measurements. In 22 asthmatic patients, BAL and bronchial biopsies were also performed for the assessment of the above-mentioned variables, measurement of remodelling indices and immunostaining for different activin A receptors.

Results: Sputum activin A (pg/mL) was higher in patients with SRA (median (interquartile ranges): 76 (33-185)) compared to mild-to-moderate asthma (44 (18-84); P = 0.005), whereas follistatin did not differ between the two groups. BAL activin A (pg/mL) was higher in patients with SRA compared to those with mild-to-moderate disease. A significant association was observed between activin A and TGF-β1, eosinophils in sputum and/or in BAL, while reticular basement membrane (RBM) thickness was significantly associated with BAL activin levels only. No difference in immunostaining for activin receptor type IB was observed between patients with SRA and those with mild-to-moderate asthma.

Conclusion: Sputum and BAL levels of activin A are higher in SRA. The association of activin A with TGF-β1, eosinophils and RBM thickness may indicate a role of this cytokine in the inflammatory and remodelling process in SRA.

Keywords: activin A; asthma; follistatin; inflammation; remodelling.