Allergy Asthma Respir Dis.  2021 Apr;9(2):76-83. 10.4168/aard.2021.9.2.76.

Therapeutic effect of atorvastatin on interleukin-13-induced lung pathology

Affiliations
  • 1Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
  • 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 3Pulmonary, Critical Care and Sleep Medicine, Yale University, School of Medicine, New Haven, CT, USA
  • 4Department of Molecular Microbiology and Immunology, Division of Biology and Medical Sciences, Brown University, Providence, RI, USA

Abstract

Purpose
Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on the IL-13-induced lung pathology through the modulation of macrophages.
Methods
Atorvastatin (40 mg/kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, numbers of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar macrophage cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed.
Results
Significant reduction in total leukocytes and alleviation of AHR were observed with administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P< 0.05). Atorvastatin administration resulted in upregulation of IL-10 in the lungs of IL-13 TG mice (P< 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P< 0.05). M2 macrophage markers, such as Ym-1 and CD206, were decreased, while M1 macrophage marker, inducible nitric oxide synthase, was increased upon atorvastatin treatment (P< 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P< 0.05).
Conclusion
The results of this study reveal a potential of atorvastatin as an effective antiasthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.

Keyword

Asthma; interleukin-13; Atorvastatin; Antiasthmatic agents; Macrophage
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