TY - JOUR T1 - How Could Physical Activity Reduce Inflammation and Inflammatory Gene Expression in Rheumatoid Arthritis? JF - The Journal of Rheumatology JO - J Rheumatol SP - 1299 LP - 1302 DO - 10.3899/jrheum.220788 VL - 49 IS - 12 AU - Patrick H. Dessein AU - Anne E. Stanwix AU - Ahmed Solomon Y1 - 2022/12/01 UR - http://www.jrheum.org/content/49/12/1299.abstract N2 - Exposure to adverse life events and acute physical injury such as that caused by trauma or infection trigger activation of the sympathetic nervous system (SNS) in response to direct signaling from the brain.1-3 This instantly results in enhanced production of adrenaline and noradrenaline by the adrenal glands. Within minutes, the hypothalamic-pituitary-adrenal (HPA) axis is stimulated, leading to increased adrenal gland cortisol secretion. The SNS and HPA axis comprise the main components of the stress system. Stress system activation also involves reduced growth hormone, insulin-like growth factor-1 (IGF-1), androgen and thyroid hormone production, decreased vagal nerve activity, and increased renin-angiotensin-aldosterone system (RAAS) activation. The purpose of these neuroendocrine changes is to orchestrate the release of energy from its stores including the liver, adipose tissue, and muscle in the form of glucose, free fatty acids, and amino acids, and provide it to the activated immune system. This engenders an adequate inflammatory response and its subsequent resolution to reestablish homeostasis.Rheumatoid arthritis (RA) is a prototypic chronic inflammatory disease. Whereas the stress system is also activated in response to RA activity, it does not succeed in resolving the inflammatory process and is therefore unable to restore homeostasis.4 Even though cortisol levels are normal or slightly elevated in patients with RA who have not been treated with exogenous glucocorticoids (GCs), these levels appear to be too low to fully suppress the inflammatory process. This low GC level is thought to be due to cytokine-mediated desensitization of the HPA axis in RA. Additionally, some patients with RA experience GC resistance that may, at least in part, be genetically mediated. This seemingly inadequate cortisol response to RA-induced chronic inflammation may, however, serve to protect patients against persistent hypercortisolemia-induced sepsis. Still, HPA axis sensitivity to stressors other than inflammation, such as hypoglycemia stress, … Address correspondence to Dr. P.H. Dessein, Departments of Medicine and Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa. Email: patrick.dessein22{at}gmail.com. ER -