Antiasthmatic effect of atorvastatin via modulation of macrophage activation

Abstract

Purpose: Asthma is a chronic airway inflammatory disorder and is associated with macrophages. Statin, a well-known lipid-lowering agent, has recently been noted for its anti-inflammatory effect on macrophage. This study was designed to evaluate the antiasth matic effect of atorvastatin via modulation of macrophage activation by using an animal model of allergic asthma. Methods: Atorvastatin 40 mg/kg was given by gavage once a day for 3 days before challenge of ovalbumin (OVA); airway hyperre -sponsiveness (AHR), airway inflammatory cells, and cytokines were evaluated in the murine asthma model. The direct effect of ator vastatin on the activation of macrophages in vitro was determined using the alveolar macrophage cell line CRL-2456. Results: Administration of atorvastatin reduced the numbers of total inflammatory cells, macrophages, and eosinophils as well as lung histology enhanced in the murine asthma model. AHR measured by enhanced pause was significantly reduced after atorvas tatin administration in the murine asthma model (P<0.05). Atorvastatin administration resulted in the reduction in serum OVA-spe cific IgE levels and the increase in serum OVA-specific IgG2a levels (P<0.05). The mRNA levels of Ccr3, Il-17, and Muc5ac enhanced by OVA challenge were decreased by treatment with atorvastatin (P<0.05). Along with these improvement in allergic inflammatory changes, the population of CD11c-CD206+ macrophages as well as the expression of Ym-1 and Relm-α in the lungs were reduced with atorvastatin (P<0.05). In vitro test with CRL-2456 showed that atorvastatin reduced the expression of Cd206, Arg-1, and Fgf-2 in duced by IL-4 stimulation (P<0.05). Conclusion: This study highlighted the antiasthmatic effect of atorvastatin on the suppression of M2 macrophage activation in al lergic asthma. (Allergy Asthma Respir Dis 2021;9:27-35)