title: Disrupted TH17/Treg balance in patients with chronic low back pain.
abstract: Chronic low back pain (CLBP) is a leading cause of disability and costs in health care systems worldwide. Despite extensive research, the exact pathogenesis of CLBP, particularly the individual risk of chronification remains unclear. To investigate a possible role of the adaptive immune system in the pathophysiology of CLBP, we analyzed T cell related cytokine profiles, T cell related mRNA expression patterns and the distribution of T cell subsets in 37 patients suffering from nonspecific CLBP before and after multimodal therapy in comparison to 25 healthy controls. Serum patterns of marker cytokines were analyzed by Luminex technology, mRNA expression of cytokines and specific transcription factors was measured by real-time PCR, and distribution of TH1-, TH2-, TH17- and regulatory T cell (Tregs) subsets was determined by multicolor flow cytometry. We found that CLBP patients exhibit an increased number of anti-inflammatory Tregs, while pro-inflammatory TH17 cells are decreased, resulting in an altered TH17/Treg ratio. Accordingly, FoxP3 and TGF-β-mRNA expression was elevated, while expression of IL-23 was reduced. Serum cytokine analyses proved to be unsuitable to monitor the adaptive immune response in CLBP patients. We further show that even after successful therapy with lasting reduction of pain, T cell subset patterns remained altered after a follow-up period of 6 months. These findings suggest an involvement of TH17/Treg cells in the pathogenesis of CLBP and emphasize the importance of these cells in the crosstalk of pain and immune response.
  
  
  BACKGROUND
  German Clinical Trial Register: Registration Trial DRKS00005954.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Luchting
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Banafscheh
authors.initials: B
authors.lastname: Rachinger-Adam
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Zeitler
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Egenberger
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Möhnle
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kreth
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Shahnaz Christina
authors.initials: SC
authors.lastname: Azad
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D017116:Low Back Pain / Q000276:immunology* / Q000628:therapy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger