Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems

Ann Rheum Dis. 2006 Jan;65(1):51-6. doi: 10.1136/ard.2005.038059. Epub 2005 Jun 7.

Abstract

Objective: To study in parallel the outflow of the sympathetic nervous system (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods: 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide Y (NPY) was used to evaluate the sympathetic outflow.

Results: Patients with SLE had increased NPY levels in comparison with HS, irrespective of prior prednisolone treatment (p<0.001). For patients with RA, only those with prednisolone treatment had increased NPY levels in comparison with HS (p = 0.016). Daily prednisolone dose correlated positively with serum NPY in RA (R(Rank) = 0.356, p = 0.039). In contrast, plasma ACTH levels were generally decreased significantly in comparison with HS in SLE with prednisolone, and in RA with/without prednisolone. Similarly, serum cortisol levels were also decreased in SLE with/without prednisolone, and in RA with prednisolone. The NPY/ACTH ratio was increased in SLE and RA, irrespective of prior prednisolone treatment. The NPY/cortisol ratio was increased in SLE with/without prednisolone, and in RA with prednisolone. Twelve weeks' anti-TNF antibody treatment with adalimumab did not decrease NPY levels in RA, irrespective of prednisolone treatment.

Conclusions: An increased outflow of the SNS was shown and a decreased tone of the HPA axis in patients with SLE and RA. Low levels of cortisol in relation to SNS neurotransmitters may be proinflammatory because cooperative anti-inflammatory coupling of the two endogenous response axes is missing.

MeSH terms

  • Adalimumab
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / physiopathology*
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Middle Aged
  • Neuropeptide Y / blood*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiopathology*
  • Prednisolone / therapeutic use
  • Severity of Illness Index
  • Sympathetic Nervous System / physiopathology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • Neuropeptide Y
  • Tumor Necrosis Factor-alpha
  • Adrenocorticotropic Hormone
  • Prednisolone
  • Adalimumab
  • Hydrocortisone