The anti-asthmatic potential of Rho-kinase inhibitor hydroxyfasudil in the model of experimentally induced allergic airway inflammation

Objective: This experimental study evaluated the anti-asthmatic potential of the Rho-kinase inhibitor hydrox-yfasudil in the settings of allergen-induced allergen-induced experimental asthma. Methods: Chronic allergic airway inflammation was caused by 28 days-sensitisation of guinea pigs with oval-bumin (OVA). Hydroxyfasudil was administered intraperitoneally in two doses for the last two weeks (1 mg/kg b. w.; 10 mg/kg b.w.). The degree of allergic inflammation was determined based on concentrations of inflam-matory Th2 cytokines (IL-4, IL-13), Th1 cytokines (TNF-alpha and IFN-gamma) in the lung homogenate and leukocyte count in the bronchoalveolar lavage fluid (BALF). The markers of remodelling and fibrosis, the growth factors (TGF-81, EGF), EGF receptor, collagen type III and V were estimated in lung homogenate. The changes in specific airway resistance (sRaw) were used as an in vivo bronchial hyperreactivity parameter.Results: Hydroxyfasudil administration at both doses significantly reduced sRaw after a week of therapy. We observed a decline of IL-13, TNF-alpha and IFN-gamma in lung homogenate and a lower presence of lymphocytes in BALF after 14 days of hydroxyfasudil administration at both tested doses. Hydroxyfasudil 14 days-treatment at both doses effectively reduced the concentrations of TGF-81, EGF receptors, collagen type III and V in BALF and modulated EGF levels. Conclusions: These findings indicate that RhoA/Rho-kinase is involved in the pathophysiology of allergic airway inflammation and suggest that Rho-kinase inhibitor hydroxyfasudil has therapeutic potential for asthma management.