qRT-PCR of Inflammatory Mediators in Brain of Etanercept and mifepristone treatment in Gulf War Illness model

Over 30% of veterans of the 1990-91 Gulf War experience a chronic multi-symptom disorder, Gulf War Illness, that has been associated with underlying persistent neuroinflammation as a result of chemical and physiological exposures experienced during deployment. Current research is largely focused on identifying effective treatment strategies for the underlying cause of Gulf War Illness instead of treating specific sets of symptoms. Through the computational evaluation of blood biomarkers and gene expression in veterans with Gulf War Illness, we previously identified that a combination of anti-inflammatory and anti-glucocorticoid treatment may prove effective in treating the underlying neuroimmune dysfunction associated with Gulf War Illness. Here, we have evaluated combined treatment with the anti-TNFα drug, etanercept, and anti-glucocorticoid, mifepristone, in an established long-term mouse model of Gulf War Illness of combined physiological stress and nerve agent exposure. Supporting the computational modeling of this treatment, we found that this drug combination significantly alleviates the underlying neuroinflammation associated with Gulf War Illness. The fusion of computational and in vivo preclinical treatment evaluation may provide a highly useful and translationally-relevant means by which to identify successful treatment paradigms for Gulf War Illness.

1990至1991年海湾战争退伍军人中，超过30%罹患慢性多症状紊乱——海湾战争综合征（Gulf War Illness），该疾病与部署期间接触化学物质及生理应激所引发的持续性神经炎症密切相关。当前相关研究主要聚焦于针对海湾战争综合征的根本病因开发有效治疗策略，而非仅针对特定症状群开展干预。本团队此前通过对海湾战争综合征退伍军人的血液生物标志物及基因表达进行计算分析，发现抗炎与抗糖皮质激素联合疗法或可有效改善该疾病相关的潜在神经免疫功能异常。本研究针对已构建的、结合生理应激与神经毒剂暴露的海湾战争综合征长期小鼠模型，评估了抗TNFα药物依那西普（etanercept）与抗糖皮质激素米非司酮（mifepristone）的联合治疗效果。该结果印证了此前的计算模型预测，本团队发现此种药物联合疗法可显著缓解海湾战争综合征相关的潜在神经炎症。将计算分析与体内（in vivo）临床前治疗评估相结合的研究范式，或可为开发有效的海湾战争综合征治疗方案提供极具实用价值且具备临床转化相关性的可行路径。