Sun J, Wong B, Cundall M, Goncharova S, Conway M, Dalrymple A, Coyle A J, Waserman S, Jordana M
Department of Pathology and Molecular Medicine and Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
Clin Exp Allergy. 2007 Jun;37(6):901-8. doi: 10.1111/j.1365-2222.2007.02723.x.
Seasonal rhinitis is manifested by a series of nasal symptoms in response to exposure to seasonal allergens including ragweed pollen. Understanding its immunological mechanisms may help to better manage the disease.
We sought to determine comprehensively ragweed-induced cytokine and chemokine production by peripheral blood mononuclear cells from normal individuals and patients with seasonal rhinitis sensitized to ragweed pollen, and to assess its regulation by exogenous IL-10.
Cells were cultured in the presence or absence of a purified ragweed pollen extract with or without exogenous IL-10. Cytokines and chemokines were measured in the supernatant. Gene expression was evaluated using real-time quantitative reverse transcription PCR.
Ragweed stimulation significantly increased the production of the Th2-associated cytokines IL-5, IL-9 and IL-13, the chemokines CCL17 and CCL22 and the regulatory cytokine IL-10 in allergic patients, whereas transforming growth factor-beta (TGF-beta) production was increased only in normal individuals. No difference was detected between groups in the production of the Th1 cytokine IFN-gamma or the Th1-affiliated chemokines CXCL10 and CXCL11. Exogenous IL-10 significantly suppressed spontaneous and induced production of both Th1- and Th2-associated cytokines and chemokines.
Our work demonstrated that locally manifested allergic rhinitis is underlined by a systemic Th2 immune response specific to allergens. The molecular pathogenesis of allergic rhinitis may be linked to a compromised allergen-specific immune regulation, e.g., reduced spontaneous and allergen-induced TGF-beta production in patients compared with healthy controls. Our data also show that IL-10 inhibits both the effector and directional mechanisms of allergen-specific immune response, further supporting its potential therapeutic benefit in preventing and treating allergic diseases.
季节性鼻炎表现为一系列鼻部症状，是对包括豚草花粉在内的季节性过敏原暴露的反应。了解其免疫机制可能有助于更好地管理该疾病。
我们试图全面确定豚草诱导正常个体和对豚草花粉致敏的季节性鼻炎患者外周血单核细胞产生细胞因子和趋化因子的情况，并评估外源性白细胞介素-10对其的调节作用。
细胞在有或无纯化豚草花粉提取物以及有或无外源性白细胞介素-10的情况下进行培养。测定上清液中的细胞因子和趋化因子。使用实时定量逆转录聚合酶链反应评估基因表达。
豚草刺激显著增加了过敏性患者中与Th2相关的细胞因子白细胞介素-5、白细胞介素-9和白细胞介素-13、趋化因子CCL17和CCL22以及调节性细胞因子白细胞介素-10的产生，而转化生长因子-β（TGF-β）的产生仅在正常个体中增加。两组在Th1细胞因子干扰素-γ或与Th1相关的趋化因子CXCL10和CXCL11的产生上未检测到差异。外源性白细胞介素-10显著抑制了Th1和Th2相关细胞因子及趋化因子的自发和诱导产生。
我们的研究表明，局部表现的过敏性鼻炎以针对过敏原的全身性Th2免疫反应为基础。过敏性鼻炎的分子发病机制可能与过敏原特异性免疫调节受损有关，例如与健康对照相比，患者中自发和过敏原诱导的TGF-β产生减少。我们的数据还表明，白细胞介素-10抑制过敏原特异性免疫反应的效应和定向机制，进一步支持其在预防和治疗过敏性疾病方面的潜在治疗益处。
