Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
Agogo Presbyterian Hospital, Agogo, Ghana.
Infection. 2023 Feb;51(1):169-179. doi: 10.1007/s15010-022-01870-3. Epub 2022 Jun 27.
Mycobacterium (M.) tuberculosis-caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and recovery.
In this study, we analyzed the concentrations of selected plasma cytokines (i.e., IL-6, IP-10, IL-10, IL-22, IFNγ, GM-CSF, IL-8) and M. tuberculosis sputum burden in patients with tuberculosis (n = 76). Cytokine levels were compared to healthy contacts (n = 40) and changes under treatment were monitored (i.e., 6 and 16 weeks after treatment start). According to differences in M. tuberculosis sputum burden and conversion, tuberculosis patients were classified as paucibacillary as well as 'rapid' or 'slow' treatment responders. A subgroup of tuberculosis patients had fatal disease courses.
Six of seven cytokines were significantly higher in tuberculosis patients as compared to contacts and four of these (i.e., IL-6, IP-10, IL-10, and IL-22) were detectable in the majority of tuberculosis patients. IL-6 showed the strongest discriminating capacity for tuberculosis disease and in combination with IL-10 concentrations efficiently classified paucibacillary tuberculosis cases as well as those with fatal disease outcome. In addition, IL-6 and IP-10 levels decreased significantly after 6 weeks of treatment and analyses of subgroups with differential treatment response showed delayed decline of IL-6 levels in slow treatment responders.
Combinations of different plasma cytokine (namely, IL-6, IL-10, and IP-10) efficiently classified tuberculosis patients with differential mycobacterial burden and especially IL-6 qualified as a biomarker candidate for early treatment response.
结核分枝杆菌（M. tuberculosis）引起的免疫病理学的特征是人类结核病中血浆细胞因子的异常表达。疾病的严重程度和长期抗分枝杆菌治疗可能受到免疫病理学的影响，治疗过程中血浆细胞因子水平的正常化可能表明治疗效果和恢复情况。
在这项研究中，我们分析了 76 例结核病患者（简称 TB 患者）选定的血浆细胞因子（即 IL-6、IP-10、IL-10、IL-22、IFNγ、GM-CSF、IL-8）和结核分枝杆菌痰负荷的浓度。将细胞因子水平与健康接触者（简称 HC，n=40）进行比较，并监测治疗过程中的变化（即治疗开始后 6 和 16 周）。根据结核分枝杆菌痰负荷和转化的差异，将 TB 患者分为少菌型和“快速”或“缓慢”治疗应答者。TB 患者的亚组发生了致命的疾病过程。
与 HC 相比，7 种细胞因子中有 6 种在 TB 患者中显著升高，其中 4 种（即 IL-6、IP-10、IL-10 和 IL-22）在大多数 TB 患者中可检测到。IL-6 对结核病疾病具有最强的区分能力，与 IL-10 浓度相结合，能够有效地将少菌型结核病病例以及具有致命疾病结局的病例进行分类。此外，在治疗 6 周后，IL-6 和 IP-10 水平显著降低，对不同治疗反应的亚组分析表明，在缓慢治疗应答者中，IL-6 水平的下降延迟。
不同血浆细胞因子（即 IL-6、IL-10 和 IP-10）的组合有效地对具有不同分枝杆菌负担的 TB 患者进行分类，特别是 IL-6 可作为早期治疗反应的候选生物标志物。
