Tsilibary Effie-Photini C, Carlson Danielle, Georgopoulos Apostolos P
Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
J Neurol Neuromedicine. 2021 Aug 20;6(1):26-31. doi: 10.29245/2572.942x/2021/1.1281.
Gulf War Illness (GWI) afflicted many veterans of the 1990-91 Gulf War with multiple symptoms worsening with time. The reasons for GWI have not been elucidated but may include toxicity due to inflammatory factors induced by vaccines administered to deployed and nondeployed veterans. In particular, the anthrax vaccine may have harmful effects in veterans lacking specific protective HLA alleles, as we reported previously, using a murine neuroblastoma N2A cell culture system. Lack of these protective alleles could allow several vaccine antigens to circulate chronically, resulting in protracted low-grade inflammation accompanying the disease. When N2A cells were exposed to GWI serum or the antigen of the anthrax vaccine, the cells underwent apoptosis due to compromised cell membrane, mitochondrial and cytoskeletal function. Elucidation of mechanisms of GWI should provide clues for therapy. Since antigen-induced inflammation accompanies GWI and stem cells were reported to have antimicrobial activity, we examined the effect of murine stem cells co-cultured with N2A cells before exposure to GWI serum and also Protective Antigen PA63, the main component of the anthrax vaccine. The presence of stem cells completely prevented GWI serum toxicity, since it resulted in inhibition of apoptosis. Moreover, cultures of stem cells exposed to PA63 resulted in the degradation of this antigen. We conclude that stem cells can protect against vaccine-induced toxic components of the GWI serum in N2A cells, prompting further studies on the possible beneficial effects of these cells in GWI.
海湾战争综合征（GWI）折磨着许多参加1990 - 1991年海湾战争的退伍军人，其多种症状随时间恶化。GWI的病因尚未阐明，但可能包括部署和未部署的退伍军人接种疫苗所诱导的炎症因子导致的毒性。特别是，正如我们之前在小鼠神经母细胞瘤N2A细胞培养系统中所报道的，炭疽疫苗可能对缺乏特定保护性HLA等位基因的退伍军人产生有害影响。缺乏这些保护性等位基因可能会使几种疫苗抗原长期循环，导致伴随该疾病的长期低度炎症。当N2A细胞暴露于GWI血清或炭疽疫苗抗原时，由于细胞膜、线粒体和细胞骨架功能受损，细胞会发生凋亡。阐明GWI的机制应为治疗提供线索。由于抗原诱导的炎症伴随着GWI，并且据报道干细胞具有抗菌活性，我们在N2A细胞暴露于GWI血清以及炭疽疫苗的主要成分保护性抗原PA63之前，研究了与N2A细胞共培养的小鼠干细胞的作用。干细胞的存在完全预防了GWI血清毒性，因为它导致了凋亡的抑制。此外，暴露于PA63的干细胞培养物导致了该抗原的降解。我们得出结论，干细胞可以保护N2A细胞免受GWI血清中疫苗诱导的毒性成分的影响，这促使我们进一步研究这些细胞在GWI中可能的有益作用。
