The development of an animal model of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe multisystem disease characterized by unexplained fatigue that is not alleviated by rest, is greater than 6 months in duration, and has a detrimental impact on function and quality of life. Further, ME/CFS is associated with several symptoms including pain, anxiety/stress, cognitive difficulties, and post-exertional malaise. The pathobiological mechanisms underlying the induction and maintenance of ME/CFS remain poorly understood. This is reflected in the small number of potential mouse models described in the literature, lack of available biomarkers, and multiple hypothesized mechanisms across body systems. Up to 80% of individuals with ME/CFS report their disease began with an acute infection suggesting an immune component as a trigger. In individuals with ME/CFS, there is considerable evidence for immune system dysfunction with a general increase in inflammatory cytokines and altered expression of immune cell phenotypes. However, prior studies have been small, only considered a few cytokines or immune cell types, and have not adequately assessed multiple variables across the biopsychosocial spectrum. Thus, the relationship between clinical symptoms and immune system changes are unknown. Stress is strongly associated with the development of ME/CFS. Acute stress can enhance the inflammatory response of the immune system, suggesting that stress could serve as a priming event to ME/CFS development. The overall goal of this work was to build a clinically relevant animal model of ME/CFS utilizing stress and immune activation. I proposed that stress combined with an acute infection leads to alterations in immune function resulting in elevated risk for the development of persistent fatigue.