Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, Tunis, Tunisia; Tunis El Manar University, Tunis 1068, Tunisia.
Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, Tunis, Tunisia; Faculty of Medicine of Tunis, 1006, Tunisia; Tunis El Manar University, Tunis 1068, Tunisia.
Cytokine. 2024 Jul;179:156617. doi: 10.1016/j.cyto.2024.156617. Epub 2024 Apr 16.
Remitting-Relapsing Multiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuro-inflammatory disorders leading to brain damage and disability in young adults. Herein, we investigated in these patients the cytokine response by beads-based multiplex assays during the early stages of these disorders. Cytokine investigations were carried out on treatment-naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that Cerebrospinal Fluid (CSF) cells from NBD patients, but not RRMS, secrete significant high levels of IL-22 which is associated with elevated IL-22 mRNA expression. We also observed an increase in IL-22 levels in the definite NBD subgroup as compared to the probable NBD one, indicating a clear relationship between elevated IL-22 levels and diagnostic certainty. Interestingly, we found no correlation of IL-22 secretion between CSF and serum arguing about intrathecal release of IL-22 in the CNS of NBD patients. Moreover, we showed by correlogram analysis that this cytokine doesn't correlate with IL-17A, IL-17F and IL-21 suggesting that this cytokine is secreted by Th22 cells and not by Th17 cells in the CSF of NBD patients. Finally, we found elevated levels of IL-6 and a positive correlation between IL and 6 and IL-22 in the CSF of NBD. In conclusion, these results suggest that IL-6 contributes to the production of IL-22 by T cells leading to the exacerbation of inflammation and damage within the CNS of NBD patients.
缓解-复发型多发性硬化症 (RRMS) 和神经白塞病 (NBD) 是两种导致年轻人脑损伤和残疾的慢性神经炎症性疾病。在此,我们研究了这些患者在这些疾病早期阶段的细胞因子反应。细胞因子研究是针对首次临床复发时患有 RRMS 和 NBD 的未经治疗的患者进行的。我们的研究结果表明,NBD 患者的脑脊液 (CSF) 细胞而非 RRMS 细胞分泌高水平的 IL-22,这与升高的 IL-22 mRNA 表达有关。我们还观察到,与可能的 NBD 亚组相比,明确的 NBD 亚组的 IL-22 水平增加,表明升高的 IL-22 水平与诊断确定性之间存在明确的关系。有趣的是,我们发现 CSF 和血清之间的 IL-22 分泌没有相关性,这表明 NBD 患者中枢神经系统中存在 IL-22 的鞘内释放。此外,我们通过相关图分析表明,这种细胞因子与 IL-17A、IL-17F 和 IL-21 不相关,这表明这种细胞因子是由 Th22 细胞而不是 Th17 细胞在 NBD 患者的 CSF 中分泌的。最后,我们发现 NBD 的 CSF 中 IL-6 水平升高,IL-6 和 IL-22 之间呈正相关。总之,这些结果表明,IL-6 有助于 T 细胞产生 IL-22,从而加剧 NBD 患者中枢神经系统内的炎症和损伤。