The Autonomic Nervous System and the Immune System in Juvenile Rheumatoid Arthritis

This study demonstrates that juvenile rheumatoid arthritis is associated with a dysregulation of the autonomic nervous system as well as with disturbances in the capacity of the immune system to respond to mediators of the autonomic nervous system. In patients with active disease heart rate at rest is higher than in healthy controls. In addition, 3-hydroxy-4-phenoxyphenylglycol levels in urine are higher in all patients than in the control group. Cardiovascular responses to an orthostatic stress test (tilt up) are reduced in patients with active and nonactive disease. Plasma norepinephrine responses to tilt up are reduced in subjects with active juvenile rheumatoid arthritis. In summary, our data show that patients with juvenile rheumatoid arthritis have an altered function of the autonomic nervous system associated with increased central noradrenergic outflow, presumably leading to increased vasoconstriction, resulting in a decreased response to an orthostatic stressor. The altered function of the autonomic nervous system is associated with changes in the response of leukocytes to mediators of the autonomic nervous system via β2-adrenergic receptors. Leukocytes of patients with active juvenile rheumatoid arthritis have a lower cAMP response to a β2-adrenergic agonist, presumably due to increased cAMP–phosphodiesterase activity in these cells.