title: Role of neuroendocrine and neuroimmune mechanisms in chronic inflammatory rheumatic diseases--the 10-year update.
abstract: BACKGROUND
  Neuroendocrine immunology in musculoskeletal diseases is an emerging scientific field. It deals with the aspects of efferent neuronal and neurohormonal bearing on the peripheral immune and musculoskeletal systems. This review aims to add new information that appeared since 2001.
  
  
  METHODS
  The following PubMed search sentence was used to find a total of 15,462 references between 2001 and March 2013: "(rheum* OR SLE OR vasculitis) AND (nerve OR hormone OR neurotransmitter OR neuropeptide OR steroid)." In a continuous process, year by year, this search strategy yielded relevant papers that were screened and collected in a database, which build the platform of this review.
  
  
  RESULTS
  The main findings are the anti-inflammatory role of androgens, the loss of androgens (androgen drain), the bimodal role of estrogens (support B cells and inhibit macrophages and T cells), increased conversion of androgens to estrogens in inflammation (androgen drain), disturbances of the gonadal axis, inadequate amount of HPA axis hormones relative to inflammation (disproportion principle), biologics partly improve neuroendocrine axes, anti-corticotropin-releasing hormone therapies improve inflammation (antalarmin), bimodal role of the sympathetic nervous system (proinflammatory early, anti-inflammatory late-most probably due to catecholamine-producing local cells), anti-inflammatory role of alpha melanocyte-stimulating hormone, vasoactive intestinal peptide, and the Vagus nerve via α7 nicotinergic receptors. Circadian rhythms of hypothalamic origin are responsible for circadian rhythms of symptoms (neuroimmune link revealed). Important new pain-sensitizing immunological pathways were found in the last decade.
  
  
  CONCLUSIONS
  The last decade brought much new information that gave birth to the first therapies of chronic inflammatory diseases on the basis of neuroendocrine immune targets. In addition, a new theory linked evolutionary medicine, neuroendocrine regulation of distribution of energy-rich fuels, and volume regulation that can explain many disease sequelae in patients with chronic inflammatory diseases.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital, Regensburg, Germany. Electronic address: rainer.straub@klinik.uni-regensburg.de.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Alfonse
authors.initials: A
authors.lastname: Masi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
mesh_terms: D002908:Chronic Disease; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000378:metabolism*; D012216:Rheumatic Diseases / Q000276:immunology / Q000378:metabolism*
keywords: Hormones; Nervous system; Neuroendocrine immunology; Neurotransmitters; Rheumatic diseases