Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo
Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo
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DOI：
10.1111/j.1365-2222.1997.tb00670.x
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发表时间：
1997-01-01
影响因子：
6.1
通讯作者：
Sterk, PJ
中科院分区：
文献类型：
--
作者：
Grunberg, K;Timmers, MC;Sterk, PJ
背景 哮喘加重与呼吸道病毒感染密切相关。然而，此类感染对哮喘的病理生理学后果尚不清楚。 目的 研究鼻病毒 16 (RV16) 感染对气道对组胺过敏以及鼻灌洗中白细胞介素 8 (IL-8) 的影响。 方法 27 名不吸烟的特应性轻度哮喘受试者参加了一项研究 安慰剂对照的平行研究。经鼻给予0.5-2.9 x 10(4) TCID50 RV16或安慰剂的剂量。在整个研究过程中通过问卷记录感冒症状。在进入时以及接种后第4天和第11天进行组胺激发。在进入时以及第2天和第9天进行鼻灌洗。通过PC20测量对组胺的反应（变化表示为双倍剂量：DD）。通过ELISA获得IL-8水平，并以ng/ml表示。 结果通过鼻灌洗培养物和/或每个RV16治疗受试者中抗体滴度的升高证实RV感染。在 19 名接受 RV16 治疗的受试者中，有 8 名出现严重感冒症状。在研究期间，任一治疗组的基线 FEV(1) 均未发生显着变化 (P = 0.99)。然而，在接受 RV16 治疗的受试者中，第 4 天时 PC20 下降，这在重感冒患者中最为明显（平均变化 +/- SEM：-1.14 +/- 0.28 DD，P = 0.01）。此外，RV16 组的 IL-8 水平在第 2 天和第 9 天增加（P < 0.001）。第 2 天鼻腔 IL-8 的增加与第 4 天 PC20 的变化显着相关（r = -0.48，P = 0.04）。结论我们得出结论，由实验性 RV16 感染引起的感冒的严重程度是哮喘患者气道对组胺过敏性增加的决定因素。我们的结果表明，这可能是由炎症机制介导的，涉及趋化因子（如 IL-8）的释放。
Background Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear.Objective To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine, and on interleukin-8 (IL-8) in nasal lavage.Methods Twenty-seven non-smoking atopic, mildly asthmatic subjects participated in a placebo-controlled, parallel study. A dose of 0.5-2.9 x 10(4) TCID50 RV16 or placebo was nasally administered. Cold symptoms were recorded by questionnaire throughout the study. Histamine challenges were performed at entry, and on days 4 and 11 after inoculation. Nasal lavages were obtained at entry, and on days 2 and 9. The response to histamine was measured by PC20 (changes expressed as doubling doses: DD). IL-8 levels were obtained by ELISA, and were expressed in ng/ml.Results RV infection was confirmed by culture of nasal lavage and/or by antibody titre rise in each of the RV16-treated subjects. Among the 19 RV16-treated subjects, eight developed severe cold symptoms. Baseline FEV(1) did not change significantly during the study in either treatment group (P = 0.99). However, in the RV16-treated subjects there was a decrease in PC20 at day 4, which was most pronounced in those with a severe cold (mean change +/- SEM: -1.14 +/- 0.28 DD, P = 0.01). In addition, IL-8 levels increased in the RV16 group at days 2 and 9 (P < 0.001). The increase in nasal IL-8 at day 2 correlated significantly with the change in PC20 at day 4 (r = -0.48, P = 0.04).Conclusion We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an inflammatory mechanism, involving the release of chemokines such as IL-8.