Increase of sympathetic outflow measured by NPY and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with SLE and RA – Another example of uncoupling of response systems

Objective: Short-term inflammation stimulates the sympathetic nervous system (SNS) and the hypothalamic – pituitary – adrenal (HPA) axis. The activity of the HPA axis is reduced in chronic inflammatory diseases, however, the behavior of the SNS is not similarly understood. This study was initiated to study in parallel the tone of both endogenous response system in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: A total of 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. In order to measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide Y (NPY), a relatively stable sympathetic co-transmitter of norepinephrine, was used to evaluate the sympathetic outflow. Results: SLE patients demonstrated increased NPY levels as compared to HS irrespective of prior prednisolone treatment (p<0.001). In RA patients, only those with prednisolone (pred) treatment demonstrated increased NPY levels as compared to HS (p=0.016). Daily prednisolone dose correlated positively with serum NPY in RA (RRank= 0.356, p=0.039). In contrast, in SLE and RA, plasma ACTH levels were generally decreased as compared to HS which reached the significance level in SLE with pred, and in RA with/without pred. Similarly, serum cortisol levels were also decreased in SLE with/without pred, and in RA with pred. The ratio of NPY/ACTH was increased in SLE and RA irrespective of prior prednisolone treatment. The ratio of NPY/cortisol was increased in SLE with/without pred, and in RA with pred. Twelve weeks of anti-TNF antibody therapy with adalimumab did not decrease NPY levels in RA irrespective of prednisolone treatment. Conclusions: This study demonstrates an increased outflow of the SNS and a decreased tone of the HPA axis in SLE and RA patients. Low levels of cortisol in relation to SNS neurotransmitters may be proinflammatory because cooperative antiinflammatory coupling of the two endogenous response axes is missing.