Noah T L, Becker S
Division of Pulmonary Medicine and Allergy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clin Immunol. 2000 Oct;97(1):43-9. doi: 10.1006/clim.2000.4914.
The goal of this study was to determine time courses of upregulation of several chemokines in nasal secretions after inoculation of human subjects with a low dose of live respiratory syncytial virus (RSV). Healthy, nonsmoking young adults were admitted to an inpatient clinical research unit. After baseline studies, subjects were nasally inoculated with approximately 10(3) plaque-forming units of RSV (strain A2), followed by daily nasal lavages. Nasal lavage fluid (NLF) was assayed for chemokines by specific ELISA. Of 10 subjects inoculated with RSV, 3 developed clinical symptoms of upper respiratory infection and also shed virus. Among infected subjects, there was a transient postinoculation increase in interleukin-8 (IL-8) in NLF to an average of 2.7-fold compared to baseline, followed by a prolonged increase (maximum mean 5.4-fold) during virus shedding. RANTES, MIP-1alpha, and MCP-1 all increased during virus shedding only (maximum mean increases of 5.3-fold, 13-fold, and 7.2-fold, respectively). Semiquantitative RT-PCR in brushed nasal epithelial cells on day 6 after inoculation suggested upregulation of RANTES, but not IL-8, mRNA during virus shedding. We conclude that chemokines IL-8, RANTES, MIP-1alpha, and MCP-1 are all increased in nasal secretions in human RSV infection at the time of virus shedding and symptomatic illness and that the epithelium lining the nasal turbinate contributes to the increase in RANTES.
本研究的目的是确定低剂量活呼吸道合胞病毒（RSV）接种人体后，鼻腔分泌物中几种趋化因子上调的时间进程。健康、不吸烟的年轻成年人被收治入院至住院临床研究单元。在进行基线研究后，受试者经鼻腔接种约10³空斑形成单位的RSV（A2株），随后每日进行鼻腔灌洗。通过特异性酶联免疫吸附测定法检测鼻腔灌洗液（NLF）中的趋化因子。在接种RSV的10名受试者中，3人出现上呼吸道感染的临床症状并排出病毒。在受感染的受试者中，NLF中的白细胞介素-8（IL-8）在接种后短暂增加，与基线相比平均增加2.7倍，随后在病毒排出期间持续增加（最大平均增加5.4倍）。调节激活正常T细胞表达和分泌的趋化因子（RANTES）、巨噬细胞炎性蛋白-1α（MIP-1α）和单核细胞趋化蛋白-1（MCP-1）仅在病毒排出期间增加（最大平均增加分别为5.3倍、13倍和7.2倍）。接种后第6天对刷取的鼻上皮细胞进行半定量逆转录-聚合酶链反应（RT-PCR）表明，在病毒排出期间RANTES而非IL-8的mRNA上调。我们得出结论，在人类RSV感染的病毒排出和出现症状性疾病时，趋化因子IL-8、RANTES、MIP-1α和MCP-1在鼻腔分泌物中均增加，并且鼻甲内衬上皮促成了RANTES的增加。
