Musa Bolanle O P, Onyemelukwe Geoffrey C, Hambolu Joseph O, Mamman Aisha I, Isa Albarka H
Immunology Unit, Department of Medicine, ABUTH, Zaria, Nigeria.
Clin Vaccine Immunol. 2010 Apr;17(4):602-8. doi: 10.1128/CVI.00145-09. Epub 2010 Feb 3.
The pathogenesis of sickle vaso-occlusive crisis (VOC) in sickle cell disease (SCD) patients involves the accumulation of rigid sickle cells and the stimulation of an ongoing inflammatory response, as well as the stress of infections. The immune response, via cytokine imbalances and deregulated T-cell subsets, also has been proposed to contribute to the development of VOC. In this study, a panel of high-sensitivity cytokine kits was used to investigate cytokines in the sera of SCD patients in VOC. The results were compared primarily with those for stable SCD patients and secondarily with those for normal healthy people who served as controls. The cytokines studied included interleukin-2 (IL-2), IL-4, and IL-10. Lymphocyte subsets of patients with VOC were also studied and were compared with those of both control groups (20 stable patients without crisis [SCD group] and 20 normal healthy controls [NHC]). The VOC group was notable for remarkably elevated levels of IL-4, among the three cytokines tested, compared with those for the SCD and NHC groups. Patients with VOC also differed from stable SCD patients and NHC by having notably lower IL-10 levels, as well as the lowest ratio of CD4(+) to CD8(+) T cells (0.7). The patterns of the proinflammatory cytokine IL-2 did not differ between VOC and stable SCD patients, but NHC had significantly lower IL-2 levels than both the VOC and SCD groups. Our results demonstrate coexisting levels, both high and low, of TH1- and TH2-type cytokines, as well as diminished levels of T-cell subsets in VOC. These results are discussed in an effort to better understand the importance of the immune system profile in the pathogenesis of sickle cell VOC. Since the possibility that a cytokine imbalance is implicated in the pathogenesis of sickle cell crisis has been raised, our results should prompt further investigation of the host immune response in terms of TH1 and TH2 balance in sickle cell crisis.
镰状细胞病（SCD）患者镰状血管闭塞性危机（VOC）的发病机制涉及僵硬的镰状细胞的积累、持续炎症反应的刺激以及感染应激。通过细胞因子失衡和失调的T细胞亚群介导的免疫反应也被认为与VOC的发生有关。在本研究中，使用一组高灵敏度细胞因子检测试剂盒来研究VOC状态下SCD患者血清中的细胞因子。主要将结果与稳定期SCD患者的结果进行比较，其次与作为对照的正常健康人的结果进行比较。所研究的细胞因子包括白细胞介素-2（IL-2）、IL-4和IL-10。还研究了VOC患者的淋巴细胞亚群，并与两个对照组（20名无危机的稳定患者[SCD组]和20名正常健康对照者[NHC]）的淋巴细胞亚群进行了比较。与SCD组和NHC组相比，VOC组在检测的三种细胞因子中，IL-4水平显著升高。VOC患者与稳定期SCD患者和NHC的不同之处还在于，IL-10水平显著降低，以及CD4(+)与CD8(+) T细胞的比例最低（0.7）。促炎细胞因子IL-2的模式在VOC患者和稳定期SCD患者之间没有差异，但NHC的IL-2水平显著低于VOC组和SCD组。我们的结果表明，TH1型和TH2型细胞因子在VOC中同时存在高水平和低水平，以及T细胞亚群水平降低。讨论这些结果是为了更好地理解免疫系统特征在镰状细胞VOC发病机制中的重要性。由于已经提出细胞因子失衡可能与镰状细胞危机的发病机制有关，我们的结果应该促使进一步研究镰状细胞危机中宿主免疫反应的TH1和TH2平衡。
