Thanapati Subrat, Kulkarni Shruti, Shinde Tanvi, Ganu Mohini, Ganu Ashok, Jayawant Priyanka, Tripathy Anuradha S
Department of Dengue and Chikungunya, Indian Council of Medical Research-National Institute of Virology, 20-A, Dr Ambedkar Road, Pune 411 001, India.
Sanjeevan Hospital, Latur, Maharashtra, India.
Hum Immunol. 2025 Jul;86(4):111336. doi: 10.1016/j.humimm.2025.111336. Epub 2025 Jun 16.
Cytokines and chemokines play a crucial role in orchestrating the immune response to chikungunya virus (CHIKV) infection, influencing disease course and outcome. Although significant efforts have been made to understand the cytokine signatures associated with CHIKV infection, the identification of specific cytokine biomarkers across different disease stages remains incomplete.
We have assessed CHIKV-specific cytokine, chemokine profiles of 17 analytes in 50 acute chikungunya patients, 31 chronic chikungunya arthritis patients, 30 recovered individuals, and 23 healthy controls. The cytokine and chemokines were measured in the supernatant of PBMCs stimulated in vitro with inactivated chikungunya virus.
It was observed that chronic chikungunya arthritis patients exhibited significantly higher levels of IL-1β, IL-6, and GM-CSF compared to all other groups. MCP-1 levels were elevated in patient groups compared to recovered and control individuals. IL-1β emerged as a potential biomarker for chronic chikungunya arthritis based on ROC analysis. A negative correlation between IFN-γ levels and CHIKV load was observed in acute patients, suggesting its antiviral role. IL-12 levels were higher in recovered individuals compared to all other groups, while IFN-γ levels were elevated in recovered individuals compared to acute patients.
Our findings highlight IL-1β as a potential biomarker for chronic chikungunya arthritis and suggest that GM-CSF inhibition could serve as a therapeutic intervention for disease-associated chronic inflammation. The observed co-regulation of IL-12 and IFN-γ in recovered individuals needs further investigation into their role in disease resolution. These insights provide a deeper understanding of the immunopathogenesis of CHIKV infection and may contribute in future diagnostic and therapeutic strategies.
细胞因子和趋化因子在协调针对基孔肯雅病毒（CHIKV）感染的免疫反应中发挥关键作用，影响疾病进程和结果。尽管已做出重大努力来了解与CHIKV感染相关的细胞因子特征，但在不同疾病阶段识别特定的细胞因子生物标志物仍不完整。
我们评估了50例急性基孔肯雅热患者、31例慢性基孔肯雅关节炎患者、30例康复个体和23例健康对照中17种分析物的CHIKV特异性细胞因子、趋化因子谱。细胞因子和趋化因子在体外由灭活基孔肯雅病毒刺激的外周血单核细胞上清液中进行测量。
观察到慢性基孔肯雅关节炎患者的IL-1β、IL-6和GM-CSF水平显著高于所有其他组。与康复个体和对照个体相比，患者组中的MCP-1水平升高。基于ROC分析，IL-1β成为慢性基孔肯雅关节炎的潜在生物标志物。在急性患者中观察到IFN-γ水平与CHIKV载量之间呈负相关,表明其抗病毒作用。与所有其他组相比，康复个体中的IL-12水平更高，而与急性患者相比，康复个体中的IFN-γ水平升高。
我们的研究结果突出了IL-1β作为慢性基孔肯雅关节炎的潜在生物标志物，并表明抑制GM-CSF可作为针对疾病相关慢性炎症的治疗干预措施。在康复个体中观察到的IL-12和IFN-γ的共同调节需要进一步研究它们在疾病消退中的作用。这些见解为CHIKV感染的免疫发病机制提供了更深入的理解，并可能有助于未来的诊断和治疗策略。
