Sheeran P, Jafri H, Carubelli C, Saavedra J, Johnson C, Krisher K, Sánchez P J, Ramilo O
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, USA.
Pediatr Infect Dis J. 1999 Feb;18(2):115-22. doi: 10.1097/00006454-199902000-00007.
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants. The role of inflammatory mediators in the pathogenesis of RSV disease is not well-understood. The present study was designed (1) to determine whether RANTES (regulated on activation, normal T cell expressed and presumably secreted), macrophage-inflammatory protein-1-alpha (MIP-1-alpha), interleukin (IL)-6, IL-8 and IL-10 can be detected in respiratory secretions of children with RSV infection and (2) to assess whether the concentrations of these cytokines in respiratory secretions correlate with white blood cell (WBC) counts and RSV concentrations and with disease severity.
During the 1996 to 1997 RSV season, we studied prospectively 14 intubated and 14 nonintubated children hospitalized with RSV disease. Nasal wash (NW) and tracheal aspirate (TA) samples were obtained from intubated patients on Hospital Days 1, 3 and 5. NW samples were obtained from nonintubated patients on hospital days 1 and 3. Seven healthy children undergoing elective surgery served as controls. All samples were analyzed for: (1) WBC and differential counts; (2) concentrations of RANTES, MIP-1-alpha, IL-6, IL-8 and IL-10; and (3) quantitative RSV cultures, except in control patients.
RANTES, MIP-1-alpha, IL-6, IL-8 and IL-10 were detected in NW and TA samples from all children with RSV infection. The concentrations of these cytokines in samples obtained from children with RSV infection were significantly greater than those in samples obtained from control children. NW WBC counts significantly correlated with NW RANTES, IL-6, IL-8 and IL-10 concentrations, whereas TA WBC counts significantly correlated with TA IL-6, IL-8, IL-10 and MIP-1-alpha concentrations. NW RSV concentrations correlated with NW WBC counts and with NW cytokine concentrations. Among children with RSV infection nonintubated patients had greater NW WBC counts and NW RANTES concentrations than intubated patients. TA RANTES, IL-8 and IL-10 concentrations inversely correlated with clinical markers of RSV disease severity.
The presence of cytokines in NW and TA samples of children with RSV infection suggests that they have a role in mediating the respiratory tract inflammation induced by RSV. These observations could have implications for designing new therapeutic strategies directed at immunomodulation of RSV disease.
呼吸道合胞病毒(RSV)是婴儿下呼吸道疾病最常见的病因。炎症介质在RSV疾病发病机制中的作用尚未完全明确。本研究旨在:(1)确定在RSV感染儿童的呼吸道分泌物中是否能检测到调节激活正常T细胞表达和分泌因子(RANTES)、巨噬细胞炎性蛋白-1α(MIP-1α)、白细胞介素(IL)-6、IL-8和IL-10;(2)评估这些细胞因子在呼吸道分泌物中的浓度是否与白细胞(WBC)计数、RSV浓度以及疾病严重程度相关。
在1996至1997年RSV流行季节,我们前瞻性地研究了14例因RSV疾病住院的插管患儿和14例非插管患儿。插管患者在住院第1、3和5天采集鼻洗液(NW)和气管吸出物(TA)样本。非插管患者在住院第1和3天采集NW样本。7例接受择期手术的健康儿童作为对照。所有样本均进行以下分析:(1)WBC及分类计数;(2)RANTES、MIP-1α、IL-6、IL-8和IL-10的浓度;(3)RSV定量培养(对照患者除外)。
在所有RSV感染儿童的NW和TA样本中均检测到RANTES、MIP-1α、IL-6、IL-8和IL-10。RSV感染儿童样本中这些细胞因子的浓度显著高于对照儿童样本中的浓度。NW的WBC计数与NW的RANTES、IL-6、IL-8和IL-10浓度显著相关,而TA的WBC计数与TA的IL-6、IL-8、IL-10和MIP-1α浓度显著相关。NW的RSV浓度与NW的WBC计数及NW的细胞因子浓度相关。在RSV感染儿童中,非插管患者的NW的WBC计数和NW的RANTES浓度高于插管患者。TA的RANTES、IL-8和IL-10浓度与RSV疾病严重程度的临床指标呈负相关。
RSV感染儿童的NW和TA样本中存在细胞因子,提示它们在介导RSV诱导的呼吸道炎症中起作用。这些观察结果可能对设计针对RSV疾病免疫调节的新治疗策略具有启示意义。