Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; Pediatric Department, Buzzi Children's Hospital, Milano, Italy.
International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science, Università di Milano, Milano, Italy.
Cytokine. 2024 Nov;183:156744. doi: 10.1016/j.cyto.2024.156744. Epub 2024 Aug 27.
Multisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results.
Twenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1β, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis.
IP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6-12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1β, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed.
Our study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.
儿童多系统炎症综合征（MIS-C）是冠状病毒病-19 感染后的一种感染后疾病。长期随访数据表明，初始临床严重程度不一定与长期结果相关。儿童 MIS-C 的长期免疫反应仍知之甚少。我们分析了儿科 MIS-C 患者诊断时和随访期间的细胞因子谱，探讨了细胞因子表达与标准生化和激素检测结果之间的相关性。
本研究纳入了 25 例 MIS-C 患者（平均年龄 9.4±3.9 岁），他们在诊断时和 6 个月和 12 个月随访时均有完整的检测结果。选择了一些细胞因子，如 IL-9、嗜酸性粒细胞趋化因子、IP-10、MIP-1β、RANTES、MCP-1（MCAF）、TNF-α、PDGF-B、IL-4 和 MIP-1α，纳入分析。
IP-10、MCP-1（MCAF）和 MIP-1α 水平在 6-12 个月时正常或接近正常，其余细胞因子，包括 IL-9、嗜酸性粒细胞趋化因子、MIP-1β、RANTES、TNF-α、PDGF-B、IL-4，在我们最后一次随访时仍高于对照组。在诊断后 6 个月，发现甘油三酯和 HOMA-IR 与 MCP-1（MCAF）、IL-4 和嗜酸性粒细胞趋化因子呈轻度负相关。在 12 个月的随访中，我们发现皮质醇和 ACTH 水平与 PDGF-B、MIP-1α 和 TNF-α呈轻度正相关。相反，这些细胞因子与空腹血糖和 HOMA-IR 呈负相关。
我们的研究结果突出了儿科 MIS-C 患者中明显的细胞因子介导的炎症反应，与对照组相比，在 12 个月的监测期间持续升高。我们已经确定了不同细胞因子之间的各种相互关系，以及细胞因子水平升高与代谢和激素模式之间的相关性。明显的炎症反应表明其参与了急性器官损伤，而其持续存在表明其可能对长期代谢紊乱产生影响。
