EXTENDED REPORT

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

P Härle^1,*, R H Straub^1,*, R Wiest¹, A Mayer¹, J Schölmerich¹, F Atzeni², M Carrabba², M Cutolo³, P Sarzi-Puttini²

¹ Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Hospital Regensburg, Germany
² Rheumatology Unit, University Hospital L Sacco, Milan, Italy
³ Division of Rheumatology, Department of Internal Medicine and Medical Specialties, University of Genova, Italy

Correspondence to:
Dr R H Straub
Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany; rainer.straub{at}klinik.uni-regensburg.de

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.

Abbreviations: 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

Keywords: adrenal hormones; neuropeptide Y; rheumatoid arthritis; sympathetic nervous system hormones; systemic lupus erythematosus

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