Gulf War Illness (GWI) is a chronic multi-symptom disorder experienced by as many as a third of the veterans of the 1991 Gulf War; the constellation of “sickness behavior” symptoms observed in ill veterans is suggestive of a neuroimmune involvement. Various chemical exposures and conditions in theater have been implicated in the etiology of the illness. Previously, we found that GW-related organophosphates (OPs), such as the sarin surrogate, DFP, and chlorpyrifos, cause neuroinflammation. The combination of these exposures with exogenous corticosterone (CORT), mimicking high physiological stress, exacerbates the observed neuroinflammation. The potential relationship between the effects of OPs and CORT on the brain versus inflammation in the periphery has not been explored. Here, using our established GWI mouse model, we investigated the effects of CORT and DFP exposure, with or without a chronic application of pyridostigmine bromide (PB) and N,N-diethyl-meta-toluamide (DEET), on cytokines in the liver and serum. While CORT primed DFP-induced neuroinflammation, this effect was largely absent in the periphery. Moreover, the changes found in the peripheral tissues do not correlate with the previously reported neuroinflammation. These results not only support GWI as a neuroimmune disorder, but also highlight the separation between central and peripheral effects of these exposures.

海湾战争病 (GWI) 是一种慢性多症状疾病，1991 年海湾战争的退伍军人中有多达三分之一患有此病；在患病退伍军人中观察到的一系列“疾病行为”症状表明存在神经免疫参与。剧院内的各种化学品暴露和条件都与该疾病的病因有关。此前，我们发现与 GW 相关的有机磷酸酯 (OP)，例如沙林替代品、DFP 和毒死蜱，会引起神经炎症。这些暴露与外源性皮质酮（CORT）相结合，模拟高生理压力，加剧了观察到的神经炎症。 OP 和 CORT 对大脑的影响与周围炎症之间的潜在关系尚未被探索。在这里，使用我们建立的 GWI 小鼠模型，我们研究了长期应用溴化吡斯的明 (PB) 和 N ,N-二乙基间甲苯酰胺 (DEET) 的情况下，CORT 和 DFP 暴露对肝脏细胞因子的影响和血清。虽然 CORT 引发了 DFP 诱导的神经炎症，但这种效应在外周基本上不存在。此外，外周组织中发现的变化与先前报道的神经炎症无关。这些结果不仅支持 GWI 作为一种神经免疫性疾病，而且还强调了这些暴露的中枢效应和外周效应之间的区别。