Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases

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.

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype

“…In particular, IL-6 and IL-8 are well known SASP factors that can promote chronic inflammation, drive aging and increase the risk of age-related pathologies 7 . Serum levels of IL-6 in low back pain patients are higher than those measured in control patients 31 . Similarly, the levels of matrix remodeling factors MMP-1, MMP-3, and MMP-10 are elevated in degenerative disc tissue 32, 33 .…”

Biomarkers reflect differences in osteoarthritis phenotypes of the lumbar spine: the Johnston County Osteoarthritis Project

“…Per protocol, we excluded women of childbearing age and did not evaluate for factors that may influence biomarkers in the spine such as the presence of spondylolisthesis and dynamic instability, this may limit generalizability. Although we analyzed a broad spectrum of biomarkers, we did not include recently developed inflammatory biomarkers that may be more specific to IVD degeneration 40, 41 . Despite these limitations we found a difference in biomarker levels between distinct phenotypes of spine degeneration that potentially reflect a difference in pathophysiology of these important spine structures.…”

Cell therapy for the degenerating intervertebral disc

“…(11, 12, 98–100) More recently, serum biomarkers have been reported that vary with diagnosis. (101, 101, 101, 101, 102, 102) In particular, serum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects. (101, 102) Novel treatments targeting inflammation are being pursued.…”

“…(101, 101, 101, 101, 102, 102) In particular, serum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects. (101, 102) Novel treatments targeting inflammation are being pursued. (103, 104) The high levels of proinflammatory mediators found in disc tissue from patients undergoing fusion for discogenic back pain suggest that production of proinflammatory mediators within the IVD may be a major factor in the genesis of a painful lumbar disc.…”