Abstract

BackgroundMany intervertebral disc diseases cause low back pain (LBP). Proinflammatory cytokines and matrix metalloproteinases (MMPs) participate in disc pathology. In this study, we examined levels of serum cytokines and MMPs in human subjects with diagnoses of disc herniation (DH), spinal stenosis (SS), or degenerative disc disease (DDD) relative to levels in control subjects. Comparison between subjects with DH and those with other diagnoses (Other Dx, grouped from SS and DDD) was performed to elaborate a pathological mechanism based on circulating cytokine levels.MethodsStudy participants were recruited from a spine neurosurgery practice (n = 80), a back pain management practice (n = 27), or a control cohort (n = 26). Serum samples were collected before treatment and were assayed by multiplex assays for levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor-α, MMP-1, MMP-3, and MMP-9. Inflammatory and degradative mediator levels were compared for subjects with LBP and control subjects, by diagnosis and by treatment groups, controlling for effects of sex, age, and reported history of osteoarthritis. Spearman’s correlation coefficient was used to examine relationships with age, body mass index (BMI), symptom duration, and smoking history.ResultsSerum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects. Participants with LBP due to Other Dx had significantly higher levels of IL-6 than DH and controls. Serum levels of MMP-1 were significantly lower in LBP subjects, specifically those with DH, than in control subjects. Positive correlations were found between IL-6 levels and BMI, symptom duration, and age. MMP-1 levels were positively correlated with age.ConclusionsThe findings of the present clinical study are the results of the first examination of circulating cytokine levels in DDD and SS and provide evidence for a more extensive role of IL-6 in disc diseases, where patients with DDD or SS have higher serum cytokine levels than those with DH or control subjects. These findings suggest that LBP subjects have low-grade systemic inflammation, and biochemical profiling of circulating cytokines may assist in refining personalized diagnoses of disc diseases.

Highlights

  • Many intervertebral disc diseases cause low back pain (LBP)

  • IL-6 levels in subjects with LBP were found to be Discussion The goals of this study were to examine circulating levels of inflammatory and degenerative mediators associated with intervertebral disc (IVD) disease and to evaluate changes in serum levels based on clinical factors, including diagnosis, age, gender, duration of symptoms, and two features associated with poor outcomes of treatment of LBPBMI and tobacco use

  • Serum levels of IL-6 were significantly higher and levels of matrix metalloproteinase (MMP)-1 were significantly lower in participants with LBP than in control subjects

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Summary

Introduction

Many intervertebral disc diseases cause low back pain (LBP). We examined levels of serum cytokines and MMPs in human subjects with diagnoses of disc herniation (DH), spinal stenosis (SS), or degenerative disc disease (DDD) relative to levels in control subjects. As the second most common cause of physician visits in the United States, low back pain (LBP) contributes an estimated $50 billion to 100 billion in direct healthcare spending [1,2,3,4]. LBP is a complicated amalgam of multiple diseases with an unpredictable response to treatment. LBP is caused by multiple triggers with similar clinical presentation, and physical examination is rarely diagnostic. Some of the most common diagnoses for LBP include intervertebral disc herniation (DH), spinal stenosis (SS), and degenerative disc disease (DDD)

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