Modeling the dynamics of neuroendocrine-immune interactions in collagen-induced arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects about 1% of the population in the developed world, and is primarily characterized by synovial inflammation and cartilage deterioration, typically in the joints of the hands and feet (1). The hypothalamic-pituitary-adrenal (HPA) axis, a critical component of the neuroendocrine system, is thought to be an important regulator of disease activity. It has been hypothesized that adrenal insufficiency; the inability of the HPA axis to mount an adequate anti-inflammatory in response to ongoing chronic inflammation in RA might contribute to disease pathophysiology (2). In addition, circadian variation in clinical symptoms has been well documented in RA patients. Moreover, a disruption in the natural circadian rhythms of major mediators of the HPA axis, such as cortisol has been observed (3). A mechanistic understanding of the interplay between the circadian rhythms of the HPA axis and the immune system might provide useful insights into RA pathologies and optimization of treatment regimens.