Jamil Bushra, Shahid Firdaus, Hasan Zahra, Nasir Nosheen, Razzaki Tashmeem, Dawood Ghaffar, Hussain Rabia
Department of Pathology, Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800, Pakistan.
Tuberculosis (Edinb). 2007 Jul;87(4):279-87. doi: 10.1016/j.tube.2007.03.004. Epub 2007 May 29.
Several cytokines (IFN gamma, TNF alpha, IL10 and IL6) show an association with either disease localization or dissemination in tuberculosis. There are also reports of involvement of extra-pulmonary sites in tuberculosis with differential clinical severity. However, no comparative study of biomarkers across the disease severity spectrum is available. This was the purpose of the current study. Cytokines (IFN gamma, TNFalpha, IL10 and IL6) secreted in response to a panel of stimulants (PHA, LPS or mycobacterial antigens) in whole blood were determined in eighty-two tuberculosis patients. WHO criteria was applied for stratification of patients according to disease severity: disseminated and or severe disease (EPTB1; N=29); disease localized to lung parenchyma (PTB; N=32) and disease localized to peripheral sites without lung involvement (EPTB2; N=21). Mycobacterial antigens induced IFN gamma/IL10 ratio showed a direct relationship with disease severity ranking (median ratios: EPTB1=0.21; PTB=0.85; EPTB2=7.7) and the highest correlation (Spearman Rank; rho=0.673, p<0.000001). IFN gamma/IL10 ratio also rank ordered clinical severity as it relates to anatomic sites. IFN gamma/IL10 ratio may therefore provide a useful objective marker of disease severity in both pulmonary and extra-pulmonary tuberculosis.
几种细胞因子(干扰素γ、肿瘤坏死因子α、白细胞介素10和白细胞介素6)显示出与结核病的疾病定位或播散有关。也有关于肺外部位累及结核病且临床严重程度不同的报道。然而,目前尚无针对疾病严重程度全谱的生物标志物比较研究。这就是本研究的目的。对82例结核病患者测定了全血中针对一组刺激物(植物血凝素、脂多糖或分枝杆菌抗原)分泌的细胞因子(干扰素γ、肿瘤坏死因子α、白细胞介素10和白细胞介素6)。根据世界卫生组织标准,按照疾病严重程度对患者进行分层:播散性和/或重症疾病(肺外结核病1型;N = 29);局限于肺实质的疾病(肺结核;N = 32)以及局限于外周部位且无肺部受累的疾病(肺外结核病2型;N = 21)。分枝杆菌抗原诱导的干扰素γ/白细胞介素10比值与疾病严重程度分级呈直接关系(中位数比值:肺外结核病1型 =