National Institute of Virology, Pune, India.
PLoS One. 2010 Jan 14;5(1):e8709. doi: 10.1371/journal.pone.0008709.
Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines.
METHODOLOGY/PRINCIPAL FINDINGS: In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-gamma, TNF-alpha, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-gamma were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-gamma and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-gamma showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-gamma and IL-8 were positively associated with alanine transaminase levels.
CONCLUSIONS/SIGNIFICANCE: Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-gamma and IL-8 levels had greater significance than absolute values in DHF pathogenesis.
对登革热免疫发病机制的描述在很大程度上依赖于来自东南亚和美洲的数据，而印度的数据则很少。本研究描述了来自印度西部浦那的登革热病例，主要涉及临床特征和促炎细胞因子。
方法/主要发现：2005 年，372 例疑似登革热患者采用 MAC-ELISA 和 RT-PCR 进行登革热病毒（DENV）病因学检测。在医院记录临床特征。通过 ELISA 评估循环 IFN-γ、TNF-α、IL-6 和 IL-8 水平，并通过 IgM 对 IgG 比值定义继发感染。使用 SPSS 11.0 版本进行统计分析。在 372 名个体中，221 名被确认为登革热病例。三种血清型，DENV-1、2 和 3 同时流行，发现一例双重感染。在 221 例病例中，159 例表现为登革热（DF），62 例表现为登革出血热（DHF），其中 6 例为重症 DHF，1 例死于休克。皮疹、腹痛和结膜充血与 DHF 强烈相关。DF 病例 IFN-γ水平较高，DHF 病例 IL-6 和 IL-8 水平较高（p<0.05）。继发感染的三种细胞因子平均水平高于原发感染。发病后 2-5 天采集的早期样本中 IFN-γ和 IL-8 水平高于发病后 6-15 天采集的晚期样本。IFN-γ呈显著下降趋势（p=0.005），DHF 病例 IL-8 水平呈上升趋势（交互作用 p=0.059）。IL-8 水平与血小板减少显著相关，IFN-γ和 IL-8 均与丙氨酸氨基转移酶水平呈正相关。
结论/意义：皮疹、腹痛和结膜充血可能是 DHF 的预后症状。高 IL-6 和 IL-8 水平与 DHF 相关。IFN-γ和 IL-8 水平的时间趋势比 DHF 发病机制中的绝对值更有意义。
