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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
  1. P Härle1,*,
  2. R H Straub1,*,
  3. R Wiest1,
  4. A Mayer1,
  5. J Schölmerich1,
  6. F Atzeni2,
  7. M Carrabba2,
  8. M Cutolo3,
  9. P Sarzi-Puttini2
  1. 1Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Hospital Regensburg, Germany
  2. 2Rheumatology Unit, University Hospital L Sacco, Milan, Italy
  3. 3Division of Rheumatology, Department of Internal Medicine and Medical Specialties, University of Genova, Italy
  1. Correspondence to:
    Dr R H Straub
    Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany; rainer.straub{at}


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 (RRank = 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.

  • ACR, American College of Rheumatology
  • ACTH, adrenocorticotropic hormone
  • CRH, corticotropin-releasing hormone
  • HPA, hypothalamic-pituitary-adrenal
  • HS, healthy subjects
  • IL, interleukin
  • NPY, neuropeptide Y
  • RA, rheumatoid arthritis
  • SLE, systemic lupus erythematosus
  • SLEDAI, SLE Disease Activity Index
  • SNS, sympathetic nervous system
  • TNF, tumour necrosis factor
  • adrenal hormones
  • neuropeptide Y
  • rheumatoid arthritis
  • sympathetic nervous system hormones
  • systemic lupus erythematosus

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