Corticotropin-releasing factor modulates cardiovascular and pupillary autonomic reflexes in man: is there a link to inflammation-induced autonomic nervous hyperreflexia?

In two recent studies, we found autonomic nervous hyperreflexia in subjects with chronic inflammatory diseases, particularly, in those subjects with higher degrees of systemic inflammation. Since corticotropin-releasing factor (CRF) is induced by inflammatory stimuli and acts within the brain to change neuroendocrine and autonomic activity, we investigated CRF modulation of standard autonomic nervous reflexes. Fifteen healthy subjects were administered 100 microg CRF i.v., which led to a short-term increase of heart rate (p < 0.001) and a decrease in systolic and diastolic blood pressure (p < 0.050). These changes were accompanied by a reduction in heart rate variation at rest (p = 0.010) and during the respiratory sinus arrhythmia test (p = 0.019), and a reduction of pupillary latency time (p = 0.038). In further 21 normal subjects we studied the effect of prednisolone treatment on autonomic nervous function (100 mg/d during three days --> CRF reduction), which resulted in an increase of heart rate (p < 0.001), increase of heart rate variation during the respiratory sinus arrhythmia test (p < 0.001), increase in pupillary latency time (p = 0.012), a increase in maximal pupillary area (p = 0.002), and a decrease in diastolic blood pressure (p = 0.002). In conclusion, induction of a low central CRF content by prednisolone leads to a marked hyperreflexia in respiratory sinus arrhythmia and hyporeflexia in the latency time test. It is obvious that CRF can regulate autonomic reflexes. Possibly, central CRF status may also influence autonomic reflexes during chronic inflammation due to chronically changed central CRF concentration.