Chronic stress exacerbates myasthenia gravis via HPA axis-mediated immune dysregulation: Mechanisms and drug interventions.

Myasthenia gravis (MG) is a chronic, fluctuating neuromuscular disease characterised by fatigue. Patients with MG often suffer from mental stress and are prone to chronic stress responses (CSR), such as depression and anxiety. Although CSR can exacerbate MG symptoms, the precise mechanisms driving this aggravation are yet to be elucidated. In this study, we used experimental models of autoimmune MG (EAMG) and chronic unpredictable mild stress. We explored the possible mechanisms by which CSR aggravates MG symptoms and inhibits the activity of the hypothalamic-pituitary-adrenal (HPA) axis by studying the behaviour, immune function, and symptoms of experimental mice. We observed that CSR aggravated the symptoms of myasthenia in EAMG mice by enhancing the HPA axis activity and causing the inflammatory balance to shift in a proinflammatory direction. RU486, a glucocorticoid receptor antagonist, can alleviate the aggravation of CSR-induced MG symptoms by inhibiting the HPA axis activity, suggesting that the HPA axis is an important target for the treatment of CSR-related MG. This study provides a new explanation of the mechanism by which CSR aggravates MG symptoms.