interleukin-8 and Low-Back-Pain

There are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain. This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls.. We conducted a case-control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale.. Our results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.

Topics: Adult; Case-Control Studies; Cytokines; Humans; Interleukin-17; Interleukin-8; Low Back Pain; Lumbar Vertebrae; Middle Aged; Tumor Necrosis Factor-alpha

Behçet's disease (BD) is a chronic systemic vasculitis with a wide range of clinical findings. It has both autoinflammatory and autoimmune features and manifests with recurrent inflammatory attacks involving the innate immune system. Recently, autoinflammation has started to take place in the pathogenesis of intervertebral disc degeneration. The aim of this study is to evaluate the relationship between intervertebral disc degeneration and BD. We evaluated patients with BD who suffered neck or low back pain in the last 1 year. Eighty four patients underwent musculoskeletal system examination with MRI imaging of the cervical and lumbar vertebrae, and serum levels of IL6, IL8, and TNF-α were determined. The mean age was 47.7 ± 11.5 (range 20-68) years. Cervical and/or lumbar herniation was detected in the MRI imaging of 65 (77.3%) out of 84 patients. The mean IL8 levels of the group with pain and disc herniation and the group with pain and bulging were statistically significantly higher than the other groups (p = 0.007; p = 0.045, respectively). Chronic inflammation in BD may cause disc degeneration and radicular pain to begin and progress earlier in patients.

Topics: Adult; Aged; Behcet Syndrome; Humans; Interleukin-8; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Low Back Pain; Magnetic Resonance Imaging; Middle Aged; Young Adult

Degeneration of the intervertebral disc (IVD) is a major contributor to low back pain (LBP). IVD degeneration is characterized by abnormal production of inflammatory cytokines secreted by IVD cells. Although the underlying molecular mechanisms of LBP have not been elucidated, increasing evidence suggests that LBP is associated particularly with microglia in IVD tissues and the peridiscal space, aggravating the cascade of degenerative events. In this study, we implemented our microfluidic chemotaxis platform to investigate microglial inflammation in response to our reconstituted degenerative IVD models. The IVD models were constructed by stimulating human nucleus pulposus (NP) cells with interleukin-1β and producing interleukin-6 (129.93 folds), interleukin-8 (18.31 folds), C-C motif chemokine ligand-2 (CCL-2) (6.12 folds), and CCL-5 (5.68 folds). We measured microglial chemotaxis (p < 0.05) toward the conditioned media of the IVD models. In addition, we observed considerable activation of neurodegenerative and deactivation of protective microglia via upregulated expression of CD11b (p < 0.001) and down-regulation of CD206 protein (p < 0.001) by soluble factors from IVD models. This, in turn, enhances the inflammatory milieu in IVD tissues, causing matrix degradation and cellular damage. Our findings indicate that degenerative IVD may induce degenerative microglial proinflammation, leading to LBP development.

Topics: Culture Media, Conditioned; Cytokines; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Intervertebral Disc; Intervertebral Disc Degeneration; Ligands; Low Back Pain; Microglia

We showed previously that inflammatory mediators, including IL8, in intervertebral disc tissues from patients with discogenic back pain may play a key role in back pain. To investigate the molecular mechanism of IL8 signaling in back pain, we generated a mouse model that conditionally expresses human (h) IL8. We hypothesized that hIL8 levels affect mouse activity and function. Briefly, hIL8 cDNA was inserted into the pCALL2 plasmid, linearized, and injected into mouse embryos. Resulting pCALL2-hIL8 mice were then bred with GDF5-Cre mice to express the transgene in cartilage and intervertebral disc (IVD) tissues. Functional capacities including nest-making and other natural behaviors were measured. Both male and female mice expressing hIL8 showed lower nesting scores than did littermates that did not express hIL8 (

Topics: Animals; Disease Models, Animal; Female; Humans; Inflammation Mediators; Interleukin-8; Intervertebral Disc; Low Back Pain; Male; Mice; Nesting Behavior; Signal Transduction

Currently, low back disorder (LBD) research focuses primarily on mechanical variables to assess whether task demands exceed tissue capacity; however, it is important to assess how other nonmechanical variables affect tissue capacity in a time-dependent manner. The current investigation sought to explore physiological responses to an acute lifting task, as lifting has been implicated as a risk factor in the development of LBDs.. Twelve participants completed two sessions of 2 h of repetitive symmetrical lifting from floor to knuckle height under two conditions, matched for total external work (Low Force High Repetition (LFHR) and High Force Low Repetition (HFLR)). Full-body kinematics and ground reaction forces were measured throughout. Interleukin 6 (IL-6) and interleukin 8 (IL-8), markers of systemic inflammation, were assessed from blood sampling at Baseline, 0, 4 and 24 h post-lifting on both days. Dual x-ray absorptiometry (DEXA) scans were also performed on participants to quantify body composition.. Significant load (HFLR and LFHR) * time (Baseline, 0, 4, 24 h) interaction effects were found for both IL-6 and IL-8, where the LFHR condition resulted in greater responses at 0 and 4 h post-lifting.. This was the first study of its kind to concurrently measure peak and cumulative spinal moments and their relationship to systemic inflammation in both sexes, while strictly controlling for confounding variables (e.g. physical activity, caloric intake, body composition, etc.). Greater levels of IL-6 and IL-8 were seen in the LFHR condition, likely due to the greater cumulative spinal moments in this condition.

Topics: Absorptiometry, Photon; Adult; Biomechanical Phenomena; Body Composition; Cumulative Trauma Disorders; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Lifting; Low Back Pain; Male; Occupational Diseases; Spine; Stress, Physiological; Task Performance and Analysis; Weight-Bearing; Young Adult

The aim of the study was to identify inflammatory cytokines/chemokines associated with neuroinflammation and periphery-to-CNS inflammatory cross-talk in degenerative disc disease (DDD) and lumbar disc herniation (LDH), common causes of low back pain (LBP). A secondary aim was to investigate the associations between cytokines and symptom severity.. In total, 40 DDD and 40 LDH patients were recruited from a surgical waiting list, as well as 39 healthy controls (HC) and 40 cerebrospinal fluid (CSF) controls. The subjects completed questionnaires and pressure algometry was performed at the lumbar spine and forearm. The CSF, serum and disc tissues were collected during surgery. Inflammatory mediators TNF, INFg, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and MCP1 were analysed by immunoassay (Meso Scale Discovery) and quantitative real-time polymerase chain reaction (qPCR) was used for analysis of IL-6, IL-8, MCP1 and TSPO expression in intervertebral discs (IVDs).. In the LDH group, we found elevated IL-8 concentrations in CSF indicating neuroinflammation, while IL-8 and MCP1 concentrations in serum were lower compared to HC. The IVD expression of IL-6, IL-8 and TSPO was lower in LDH patients compared to DDD. LDH patients had a positive correlation between IL-8 concentrations in CSF and serum and IL-8 in CSF was associated with higher pain intensity and increased spinal pressure pain sensitivity. The MCP1 concentration in serum was associated with higher global pain ratings and increased spinal pressure pain sensitivity, while IL-6 serum concentration correlated with the intensity of the neuropathic pain component (leg pain) in LDH patients. IVD expression of TSPO in LDH patients was associated with increased intensity of back pain. No differences were found in cytokine CSF concentrations between DDD patients and CSF controls, but DDD patients had lower IL-8 and MCP1 serum concentrations than HC. In female DDD patients, IL-8 and MCP1 concentrations in serum were associated with increased intensity of back pain.. Our results suggest that neuroinflammation mediated by elevated IL-8 concentrations in CSF and IL-8 mediated periphery-to-CNS inflammatory cross-talk contributes to pain in LDH patients and suggest a link between TSPO expression in discs and low back pain.

Topics: Adult; Aged; Chemokines; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Intervertebral Disc; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Neuroimmunomodulation; Pain; Receptors, GABA

Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical. KEY MESSAGES: Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions. P. acnes can induce LBP via IL-8/CINC-1 in IVDs. P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway.

Topics: Animals; Cells, Cultured; Chemokine CXCL1; Gram-Positive Bacterial Infections; Host-Pathogen Interactions; Humans; Interleukin-8; Intervertebral Disc Degeneration; Low Back Pain; Nucleus Pulposus; Propionibacterium acnes; Rats; Signal Transduction; Toll-Like Receptor 2; Transcription Factor RelA

Low back pain (LBP) is the leading global cause of disability and is associated with intervertebral disc degeneration (DD) in some individuals. However, many adults have DD without LBP. Understanding why DD is painful in some and not others may unmask novel therapies for chronic LBP. The objectives of this study were to a) identify factors in human cerebrospinal fluid (CSF) associated with chronic LBP and b) examine their therapeutic utility in a proof-of-concept pre-clinical study.. Pain-free human subjects without DD, pain-free human subjects with DD, and patients with chronic LBP linked to DD were recruited and lumbar MRIs, pain and disability levels were obtained. CSF was collected and analyzed by multiplex cytokine assay. Interleukin-8 (IL-8) expression was confirmed by ELISA in CSF and in intervertebral discs. The SPARC-null mouse model of progressive, age-dependent DD and chronic LBP was used for pre-clinical validation. Male SPARC-null and control mice received systemic Reparixin, a CXCR1/2 (receptors for IL-8 and murine analogues) inhibitor, for 8 weeks. Behavioral signs of axial discomfort and radiating pain were assessed. Following completion of the study, discs were excised and cultured, and conditioned media was evaluated with a protein array.. IL-8 was elevated in CSF of chronic LBP patients with DD compared to pain-free subjects with or without DD. Chronic inhibition with reparixin alleviated low back pain behaviors and attenuated disc inflammation in SPARC-null mice.. These studies suggest that the IL-8 signaling pathway is a viable therapy for chronic LBP. FUND: Supported by NIH, MMF, CIHR and FRQS.

Topics: Adult; Animals; Cytokines; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Humans; Interleukin-8; Intervertebral Disc Degeneration; Low Back Pain; Magnetic Resonance Imaging; Male; Mice; Mice, Knockout; Middle Aged; Osteonectin; Signal Transduction; Sulfonamides

Earlier studies indicate that lumbar radicular pain after disc herniation may be associated with a local inflammation induced by leakage of nucleus pulposus (NP) into the spinal canal and neuroforamen. In the present study we addressed the role of two interleukins, IL-6 and IL-8 in such long-lasting lumbar radicular pain. All 127 patients were recruited from Oslo University Hospital, Ullevål, Norway. At inclusion, 6weeks and 12months, serum concentrations of IL-6 and IL-8 were analyzed by enzyme-linked immunosorbent assay (ELISA) and pain intensity was reported on a 0-10cm visual analog scale (VAS). Significantly higher levels of IL-6 and IL-8 in serum were found in patients with VAS ⩾3 at 12months, than in patient with VAS <3 at 12months (p⩽0.01, test of between-subjects effect, repeated measures ANOVA, covariates for IL-6: age, smoking; covariates for IL-8: smoking, treatment). For the first time we show that chronic lumbar radicular pain may be associated with a persistent increase of the pro-inflammatory substances IL-6 and IL-8 in serum after disc herniation.

Topics: Adult; Aged; Female; Humans; Interleukin-6; Interleukin-8; Intervertebral Disc Displacement; Low Back Pain; Male; Middle Aged; Pain Measurement; Prospective Studies

In the present study, the influence of cytokines on 1-year recovery in lumbar radicular pain was examined.. In total, 110 patients with symptomatic lumbar disc herniation were followed for 1 year. Uni- and multivariate linear regression was used to assess the influence of interleukin (IL)-6, IL-8, disc degeneration and endplate changes (Modic changes) on the changes in the Oswestry Disability Index (ODI change; primary outcome) and visual analogue scale (VAS) for low back pain (LBP) and leg pain (secondary outcomes).. Less favourable ODI outcome correlated with higher serum IL-6 levels (B = -3.41, 95% CI -5.52 to -1.30, p = 0.002), non-surgical treatment (B = -7.03, 95% CI 1.21 to 12.84, p = 0.018), higher baseline back pain intensity (B = -2.28, 95% CI -3.21 to -1.35, p < 0.001) and low educational level (B = -5.57, 95% CI 0.66 to 10.47, p = 0.027). High VAS for LBP and leg pain at 1 year was associated with high levels of serum IL-6, higher back pain intensity and longer duration of lumbar radicular pain at baseline.. High serum IL-6 levels, but not disc degeneration or Modic changes, were associated with less favourable recovery in patients with lumbar radicular pain. Intense initial back pain, non-surgical treatment, lower educational level and longer duration of radicular pain before treatment also correlated with a slower recovery the first year after disc herniation.

Topics: Adult; Cohort Studies; Educational Status; Female; Humans; Interleukin-6; Interleukin-8; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Linear Models; Low Back Pain; Magnetic Resonance Imaging; Male; Middle Aged; Orthopedic Procedures; Physical Therapy Modalities; Prognosis; Prospective Studies; Radiculopathy; Time-to-Treatment; Treatment Outcome

Topics: Cytokines; Fibromyalgia; Humans; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Longitudinal Studies; Low Back Pain; Pain Measurement; Prospective Studies; Reference Values; Tumor Necrosis Factor-alpha

This study was conducted to investigate the expression of cytokines and growth factors in disc specimens obtained from patients with herniated nucleus pulposus (HNP) and degenerated disc disease (DDD).. MRI and Western blot analyses were performed to evaluate the levels of disc degeneration and the expression levels of cytokines and growth factors.. The levels of TNF-alpha and IL-8 were significantly greater in the DDD group than in the HNP group, but no statistical differences were observed in the expression of IL-1beta, IL-6 and IL-12 between the HNP and DDD groups. In addition, the expression of TGF beta, VEGF and NGF was significantly higher in the DDD group than in the HNP group.. The greater levels of cytokine and growth factor expression in the DDD group than in the HNP explain why discogenic patients usually have more severe back pain than patients with herniated discs.

Topics: Adult; Aged; Cytokines; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Low Back Pain; Male; Middle Aged; Nerve Growth Factor; Spinal Diseases; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

An in vivo rat model of disc degeneration with emphasis on characterizing acute and chronic cytokine production.. To compare the morphologic and proinflammatory response between a single and triple-stab injury in attempts to establish mechanisms of chronic disc inflammation.. The features that distinguish physiologic (asymptomatic) from pathologic (symptomatic) degeneration are unclear. Epidemiologic evidence suggests that cumulative damage and elevated disc cytokine levels may be linked to increased low back pain rates. Although acute injury stimulates a healing response that includes transient cytokine production, repetitive damage may be necessary to trigger the persistent inflammation suspected to underlie chronic pain.. Tail discs were exposed surgically and stabbed with a number 11 blade. During the subsequent acute healing phase, triple-stab discs were percutaneously injured with a 23-gauge needle at day 3 and then again at day 6 after the initial blade incision. Cytokine (IL-1 beta, IL-6, IL-8, and TNF-alpha) production was quantified using enzyme linked immunosorbent assay, and, in addition to MAPK signaling pathways (phosphorylated forms of ERK, JNK, and p38), was localized by immunohistochemistry. Disc architecture was evaluated using histology.. Both single-stab and triple-stab discs degenerated with time, yet degeneration was more severe with repeated injury where nuclear proteoglycan was replaced by disorganized collagen. Four days after single-stab, there was a transient peak in IL-1 beta and IL-8 production that was localized to the wound track and associated granulation tissue. By contrast, triple-stab induced an activated annular fibroblast phenotype (p38 positive) that caused a prolonged, diffuse inflammatory response with elevated levels of TNF-alpha, IL-1 beta, and IL-8 up to 28 days after injury. Disc inflammation was accompanied by reactive changes in the adjacent vertebral marrow spaces that was initially lytic at day 4, becoming sclerotic by day 56.. Our results demonstrate that repeated injury during active healing leads to persistent inflammation and enhanced disc degeneration. These data support the premise that damage accumulation and its associated inflammation may distinguish pathologic from physiologic disc degeneration. In the future, this triple-stab model may be useful to evaluate the efficacy of anti-inflammatory low back pain treatments.

Topics: Acute Disease; Animals; Awards and Prizes; Chronic Disease; Cytokines; Discitis; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Interleukin-1beta; Interleukin-6; Interleukin-8; Intervertebral Disc; JNK Mitogen-Activated Protein Kinases; Low Back Pain; Lymphotoxin-alpha; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Sprague-Dawley; Spinal Diseases; Time Factors; Wound Healing; Wounds, Stab