哮喘联盟

摘要
   背景：哮喘的特征性表现是气道高反应性和气道重构。在临床上，普伐他汀和阿托伐他汀作为降胆固醇药物使用，但同时存在抗炎和免疫调节作用。
   目的：研究口服他汀类药物对气道高反应性和过敏性反应的治疗作用。
   方法：采用腹腔注射和雾化吸入卵清蛋白的方式处理BALB/c 小鼠。卵清蛋白雾化吸入激发后1周，给予胃内普伐他汀、阿托伐他汀或磷酸盐缓冲液治疗，连续2周。检测气道高反应性、血清过敏原特异性抗体水平、脾细胞和支气管肺泡灌洗液中的细胞因子含量。
   结果：普伐他汀和阿托伐他汀能有效降低气道高反应性。普伐他汀能有效抑制Th1和Th2细胞介导的抗体反应，降低血清特异性IgE、IgG、IgG1和IgG2a。普伐他汀也能有效降低IL-4、IL-5和γ干扰素的产生，但显著增加脾细胞和BALF的IL-10水平。与此类似，阿托伐他汀能有效抑制特异性IgE,、IgG1和IgG2a抗体的产生。也能显著降低脾细胞和BALF中IL-4和γ干扰素的含量，增加IL-10含量。
   结论：口服普伐他汀或阿托伐他汀不仅能抑制Th1炎症反应，而且对气道高反应性和Th2过敏反应有治疗作用。上述结果显示，这些药物有望作为非免疫抑制药治疗哮喘和过敏性疾病。

                                                                                         （刘国梁 审校）
            AnnAllergyAsthmaImmunol.2013Jan;110(1):11-7.doi:10.1016/j.anai.2012.09.002.Epub 2012 Oct 4.
 

Effect of oral administration with pravastatin and atorvastatin on airway hyperresponsiveness and allergic reactions in asthmatic mice.

Huang CF, Peng HJ, Wu CC, Lo WT, Shih YL, Wu TC.

Source
Department of Pediatrics, Tri-Service General Hospital and School of Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: h-cf@yahoo.com.tw.

Abstract
BACKGROUND: 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.
OBJECTIVE: To investigate the therapeutic effect of oral statins on airway hyperresponsiveness and allergic reaction.
METHODS: 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.
RESULTS: 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.Italso significantly attenuated IL-4,interferon γ,and increased IL-10 concentration in bronchoalveolar lavage fluid and splenocytes.
CONCLUSION: 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.

Ann Allergy Asthma Immunol. 2013 Jan;110(1):11-7. doi: 10.1016/j.anai.2012.09.002. Epub 2012 Oct 4.