Grünberg K, Timmers M C, Smits H H, de Klerk E P, Dick E C, Spaan W J, Hiemstra P S, Sterk P J
Department of Pulmonology, Leiden University Medical Centre, The Netherlands.
Clin Exp Allergy. 1997 Jan;27(1):36-45. doi: 10.1111/j.1365-2222.1997.tb00670.x.
Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear.
To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine, and on interleukin-8 (IL-8) in nasal lavage.
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.
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 RV 16-treated subjects, eight developed severe cold symptoms. Baseline FEV1, 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).
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.
哮喘急性发作与呼吸道病毒感染密切相关。然而，此类感染在哮喘中的病理生理后果在很大程度上尚不清楚。
研究鼻病毒16（RV16）感染对气道对组胺的高反应性以及对鼻腔灌洗中白细胞介素-8（IL-8）的影响。
27名不吸烟的特应性轻度哮喘患者参与了一项安慰剂对照的平行研究。经鼻腔给予0.5 - 2.9×10⁴半数组织培养感染剂量（TCID50）的RV16或安慰剂。在整个研究过程中通过问卷记录感冒症状。在入组时以及接种后第4天和第11天进行组胺激发试验。在入组时以及第2天和第9天获取鼻腔灌洗液。通过PC20（变化以加倍剂量：DD表示）测量对组胺的反应，通过酶联免疫吸附测定（ELISA）获得IL-8水平，并以ng/ml表示。
通过鼻腔灌洗培养和/或RV16治疗的每个受试者的抗体滴度升高证实了RV感染。在19名接受RV16治疗的受试者中，8人出现了严重的感冒症状。在研究期间，两个治疗组的基线第一秒用力呼气容积（FEV1）均无显著变化（P = 0.99）。然而，在接受RV16治疗的受试者中，第4天时PC20降低，在患有严重感冒的受试者中最为明显（平均变化±标准误：-1.14±0.28 DD，P = 0.01）。此外，RV16组在第2天和第9天时IL-8水平升高（P < 0.001）。第2天时鼻腔IL-8的升高与第4天时PC20的变化显著相关（r = -0.48，P = 0.04）。
我们得出结论，实验性RV16感染诱发的感冒严重程度是哮喘患者气道对组胺高反应性增加的一个决定因素。我们的结果表明，这可能是由一种炎症机制介导的，涉及趋化因子如IL-8的释放。
