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.Trial RegistrationGerman Clinical Trial Register: Registration Trial DRKS00005954.

Inflammatory biomarkers of low back pain and disc degeneration: a review

“…was characterized by elevated T reg counts with a decrease in T H 17 cell counts. This imbalance led the authors to suggest that chronic LBP is associated with immune suppression, in contrast to the notion that immune system is overactivated in LBP …”

“…CD4 + T cell lineages can be broken down into two cell subsets: T H 17 and regulatory T (T reg ) cells. Both T cell subsets have a role in the development of inflammatory diseases and were recently indicated to be involved in chronic pain . These immunological pathways exist in a paradigm in which the two T cell subsets counter one another in the formation (T H 17) or the suppression (T reg ) of autoimmunity .…”

“…This imbalance led the authors to suggest that chronic LBP is associated with immune suppression, in contrast to the notion that immune system is overactivated in LBP. 48 Disc herniation (Table 2) Some LBP studies have been performed on subjects with undefined origins of pain, and thus the findings are presented in the context of one or more diagnostic codes. Disc herniation is the most commonly presenting diagnosis in lumbar spinal diseases.…”

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

“…69, 79 Consistent with our observation of increased hemopexin in CSF of LBP patients, others have observed a reduction in Th17 T cells in LBP patients and in chronic neuropathic pain patients. 63, 64 The observation that the increase in hemopexin levels in the CSF from patients with painful DD but not in pain-free individuals with DD suggests that nerve injury may play a role in the pathophysiology of painful DD. Due to the association between nerve injury and hemopexin levels, hemopexin was selected for further analysis by ELISA.…”

The role of regulatory T cells in nervous system pathologies

“…In the clinical context, patients with chronic lower back pain showed decreased numbers of IL‐17–producing T helper cells and increased numbers of Treg cells in the blood. Accordingly, the cytokine profile revealed increased levels of FoxP3 and TGF‐β mRNA expression in peripheral blood mononuclear cells (Luchting et al, ; Luchting et al, ). A similar increase in circulating Treg cells has been observed in a range of clinical neuropathic pain conditions and has been speculated to represent an endogenous attempt to limit inflammation and subsequently reduce pain levels in affected patients (Heyn et al, ).…”