Penttila I A, Harris R J, Storm P, Haynes D, Worswick D A, Marmion B P
Department of Pathology, Adelaide University, South Australia.
QJM. 1998 Aug;91(8):549-60. doi: 10.1093/qjmed/91.8.549.
The post-Q-fever fatigue syndrome (QFS) (inappropriate fatigue, myalgia and arthralgia, night sweats, changes in mood and sleep patterns) follows about 20% of laboratory-proven, acute primary Q-fever cases. Cytokine dysregulation resulting from chronic immune stimulation and modulation by persistence of Coxiella burnetii cells or their antigens is hypothesized. We studied cytokine release patterns of peripheral blood mononuclear cells (PBMC) stimulated with various ligands in short-term culture, from 18 patients with active QFS, and 27 controls: six with resolving QFS, five who had had acute primary Q-fever without subsequent QFS, eight healthy Q-fever vaccinees and eight healthy subjects without Q-fever antibody. Conditioned media (CM) from PBMC stimulated in short-term culture with Q-fever antigens, PHA or measles antigen (as an unrelated antigen) were assayed for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN gamma by AgEIA, and for IL-1 and TNF alpha/beta by bioassay. Aberrant cytokine release patterns were observed with PBMC from QFS patients when stimulated with Q-fever antigens: an accentuated release of IL-6 which was significantly [p = 0.01, non-parametric one-way analysis of variance (ANOVA)] in excess of medians for all four control groups. With IL-2, the number of responders in the active QFS group was decreased relative to control groups (Fisher's exact test, p = 0.01) whereas the number of IFN gamma responders was increased (Fisher's exact test, p = 0.0008). Significant correlations were observed between concentrations of IL-6 in CM, total symptom scores, and scores for other key symptoms.
约20%经实验室确诊的急性原发性Q热病例之后会出现Q热后疲劳综合征（QFS）（不适当的疲劳、肌痛和关节痛、盗汗、情绪和睡眠模式改变）。据推测，慢性免疫刺激以及伯氏考克斯体细胞或其抗原持续存在所导致的调节异常会引起细胞因子失调。我们研究了短期培养中用各种配体刺激的外周血单个核细胞（PBMC）的细胞因子释放模式，这些细胞来自18例活动性QFS患者和27名对照：6例QFS正在缓解的患者、5例曾患急性原发性Q热但未继发QFS的患者、8名接种Q热疫苗的健康受试者以及8名无Q热抗体的健康受试者。用Q热抗原、PHA或麻疹抗原（作为无关抗原）在短期培养中刺激PBMC后得到的条件培养基（CM），通过酶联免疫吸附测定法（AgEIA）检测IL-2、IL-4、IL-5、IL-6、IL-10和IFNγ，并通过生物测定法检测IL-1和TNFα/β。当用Q热抗原刺激时，QFS患者的PBMC出现异常的细胞因子释放模式：IL-6释放增强，与所有四个对照组的中位数相比显著[P = 0.01，非参数单因素方差分析（ANOVA）]升高。对于IL-2，活动性QFS组的反应者数量相对于对照组减少（Fisher精确检验，P = 0.01），而IFNγ反应者数量增加（Fisher精确检验，P = 0.0008）。观察到CM中IL-6浓度、总症状评分以及其他关键症状评分之间存在显著相关性。
