Department of Pediatrics, Tri-Service General Hospital and School of Medicine, National Defense Medical Center, Taipei, Taiwan.
Ann Allergy Asthma Immunol. 2013 Jan;110(1):11-7. doi: 10.1016/j.anai.2012.09.002. Epub 2012 Oct 4.
Asthma is characterized by airway hyperresponsiveness and remodeling. Pravastatin and atorvastatin are used clinically as cholesterol-lowering agents but also exhibit anti-inflammatory and immunomodulating properties.
To investigate the therapeutic effect of oral statins on airway hyperresponsiveness and allergic reaction.
BALB/c mice received intraperitoneal sensitization and aerosol inhalation with ovalbumin consequently. One week after ovalbumin aerosol challenge, pravastatin, atorvastatin, or phosphate-buffered saline were given by intragastric gavage daily for 2 weeks. Airway hyperresponsiveness, serum allergen specific antibody levels, cytokine production by splenocytes, and bronchoalveolar lavage fluid were examined.
Both pravastatin and atorvastatin effectively reduced airway hyperresponsiveness. Pravastatin effectively suppressed both T(H)1- and T(H)2-mediated antibody responses, reducing serum specific IgE, IgG, IgG1, and IgG2a levels. Pravastatin also effectively reduced interleukin (IL) 4, IL-5, and interferon γ production but significantly enhanced IL-10 levels in splenocytes and BALF. Similarly, atorvastatin effectively attenuated production of specific IgE, IgG1, and IgG2a antibodies. It also significantly attenuated IL-4, interferon γ, and increased IL-10 concentration in bronchoalveolar lavage fluid and splenocytes.
Oral administration of pravastatin or atorvastatin not only was able to inhibit T(H)1 inflammatory responses but also had therapeutic effects on airway hyperresponsiveness and T(H)2 allergic responses. These results seem to suggest that these drugs have potential as a nonimmunosuppressive therapy for asthma and allergic diseases.
哮喘的特征为气道高反应性和重塑。普伐他汀和阿托伐他汀临床上用作降胆固醇药物，但也具有抗炎和免疫调节特性。
研究口服他汀类药物对气道高反应性和过敏反应的治疗作用。
BALB/c 小鼠接受腹腔内致敏和卵白蛋白雾化吸入。卵白蛋白雾化吸入挑战后 1 周，每天通过灌胃给予普伐他汀、阿托伐他汀或磷酸盐缓冲盐水 2 周。检查气道高反应性、血清过敏原特异性抗体水平、脾细胞细胞因子产生和支气管肺泡灌洗液。
普伐他汀和阿托伐他汀均能有效降低气道高反应性。普伐他汀能有效抑制 T(H)1 和 T(H)2 介导的抗体反应，降低血清特异性 IgE、IgG、IgG1 和 IgG2a 水平。普伐他汀还能有效降低白细胞介素（IL）4、IL-5 和干扰素γ的产生，但显著增加脾细胞和 BALF 中的 IL-10 水平。同样，阿托伐他汀能有效减弱特异性 IgE、IgG1 和 IgG2a 抗体的产生。它还显著降低了 IL-4、干扰素γ，并增加了支气管肺泡灌洗液和脾细胞中的 IL-10 浓度。
口服普伐他汀或阿托伐他汀不仅能抑制 T(H)1 炎症反应，而且对气道高反应性和 T(H)2 过敏反应具有治疗作用。这些结果似乎表明这些药物具有作为哮喘和过敏性疾病的非免疫抑制治疗的潜力。
