Imamura M, Okunishi K, Ohtsu H, Nakagome K, Harada H, Tanaka R, Yamamoto K, Dohi M
University of Tokyo, Department of Allergy and Rheumatology, Graduate School of Medicine, Tokyo, Japan.
Thorax. 2009 Jan;64(1):44-9. doi: 10.1136/thx.2007.094540. Epub 2008 Oct 3.
Statins are widely used to treat hyperlipidaemia. Their immunosuppressive effect has recently been confirmed in various immune mediated disease models. However, relatively few studies have been conducted on allergic inflammation, so the precise mechanisms of their actions against allergies have not been fully clarified. On the other hand, the role of interleukin (IL)17 in immune responses has been recently highlighted, but whether statins affect IL17 production has not been well studied. The effect of pravastatin on allergic airway inflammation in a mouse model was examined to elucidate the mechanism of action, focusing on its effect on IL17 production.
BALB/c mice were immunised with ovalbumin (OVA) and then challenged with OVA aerosol. Pravastatin was delivered by intraperitoneal injection during either sensitisation or the challenge.
When delivered during systemic sensitisation, pravastatin suppressed OVA induced proliferation and production of Th2 type cytokines such as IL5 in spleen cells ex vivo and in vitro. IL17 production was also suppressed. Furthermore, pavastatin delivered during the inhalation of OVA attenuated eosinophilic airway inflammation, OVA specific IgE production in serum and OVA induced IL17 production in the thoracic lymph node. We also found that pravastatin attenuated the antigen presenting capacity of CD11c(+) cells obtained from the OVA challenged lung.
Pravastatin suppresses the systemic sensitisation to allergen with downregulation of IL17 production. It also suppresses an ongoing immune response in the airway partly by suppressing antigen presentation in the lung. Therefore, statins could be a novel therapeutic option for treatment of asthma.
他汀类药物广泛用于治疗高脂血症。其免疫抑制作用最近在各种免疫介导疾病模型中得到证实。然而，针对变应性炎症的研究相对较少，因此其抗变态反应的确切作用机制尚未完全阐明。另一方面，白细胞介素（IL）-17在免疫反应中的作用最近受到关注，但他汀类药物是否影响IL-17的产生尚未得到充分研究。本研究检测了普伐他汀对小鼠变应性气道炎症的影响，以阐明其作用机制，重点关注其对IL-17产生的影响。
用卵清蛋白（OVA）免疫BALB/c小鼠，然后用OVA气雾剂激发。在致敏或激发期间通过腹腔注射给予普伐他汀。
在全身致敏期间给予普伐他汀，可在体内外抑制OVA诱导的脾细胞增殖及Th2型细胞因子如IL-5的产生。IL-17的产生也受到抑制。此外，在吸入OVA期间给予普伐他汀可减轻嗜酸性粒细胞性气道炎症、血清中OVA特异性IgE的产生以及OVA诱导的胸段淋巴结中IL-17的产生。我们还发现普伐他汀减弱了OVA激发的肺组织中CD11c(+)细胞的抗原呈递能力。
普伐他汀通过下调IL-17的产生抑制对变应原的全身致敏。它还部分通过抑制肺内抗原呈递来抑制气道内正在进行的免疫反应。因此，他汀类药物可能是治疗哮喘的一种新的治疗选择。
