Therapeutic Effect of Atorvastatin on Interleukin-13- Induced Lung Pathology
DOI:
https://doi.org/10.18063/jmds.v8i1.142Keywords:
Asthma, Interleukin-13, Atorvastatin, Anti-asthmatic agents, MacrophageAbstract
PPurpose: 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 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, the number of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar macrophage (AM) 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 the administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P < 0.05). Atorvastatin administration resulted in the 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 were decreased, while the M1 macrophage marker 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 the potential of atorvastatin as an effective anti-asthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.
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