Studies have revealed reduced natural killer cell function in patients with ME/CFS, which supports the findings of immune dysregulation.
34-37 A primary role of natural killer cells is to destroy virally infected cells. A defect in this response would increase susceptibility to viral infections. Additional supporting evidence is the observation of increased immune cell activation markers (CD38, HLA-DR) on CD8 cells using flow cytometry.
38 Activated CD8 cells, also called cytotoxic T cells, target damaged host cells and virally infected cells. Overactivation of CD8 cells has been linked to autoimmune diseases and supports the theory of immune dysregulation. An elevation in interleukin-1β (IL-1β), IL-12, IL-8, IL-10, and IL-13 after moderate-intensity exercise has also been observed,
39 with sustained increase in plasma tumor necrosis factor-α, in patients with ME/CFS compared with healthy controls.
39 Tumor necrosis factor-α and IL-1β are known inducers of acute-phase reactants and not typically elevated after exercise. In addition, a more exaggerated response in complement and an apparent alteration in immune cell gene expression after physical exertion, most notably toll-like receptor 4, has been uncovered.
40 Overall, these studies point to a likely involvement in immune dysregulation, resulting in secondary infections, altering the microbial trigger narrative.