Stress in autoimmune disease models

The release of endogenous glucocorticoids is critical in regulating the severity of disease activity in patients with inflammatory conditions such as rheumatoid arthritis (RA). Blocking cortisol production results in a flare-up in disease activity in RA patients, and surgical removal of the adrenals in patients with Cushing's disease has been reported to exacerbate autoimmune disease. In adjuvant-induced arthritis (AA; a rat model of RA), there is an activation of the hypothalamo-pituitary-adrenal (HPA) axis associated with the development of inflammation. In addition, there are profound changes in peptides within the paraventricular nucleus, which are responsible for regulating the HPA axis. These changes have profound implications on the ability of AA rats to respond to acute stress. Understanding the regulation of the HPA axis in health and disease holds out the promise of targeted therapy to alleviate inflammatory conditions. This article will consider the impact of stress on an individual and his or her susceptibility to inflammation. We wish to question the idea that stress is "all bad." As we shall see, exposure to a single acute stressor can alter the phenotype of the rat to change it from being susceptible to resistant in autoimmune disease models. This alteration in susceptibility takes days to manifest itself, but can last for weeks, suggesting beneficial effects of exposure to an acute stressor.