Interleukin-6 Serum Levels Are Elevated in Individuals with Degenerative Cervical Myelopathy and Are Correlated with Symptom Severity

Abstract

BackgroundFew studies have investigated systemic inflammation levels in degenerative cervical myelopathy (DCM). This study evaluated the concentration of inflammatory cytokines in DCM patients and assessed whether they can predict symptom severity.Material/MethodsA total of 40 consecutive DCM patients and 10 healthy volunteers were included in this study. Concentrations of interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α were compared between DCM patients and normal controls. Spearman’s correlation coefficient was used to examine relationships of cytokines with age, body mass index (BMI), symptom duration, and symptom severity. A DCM compression rat model was established to examine the levels of inflammatory cytokines in serum and cerebrospinal fluid (CSF).ResultsSerum level of IL-6 is significantly higher in DCM patients compared with normal people (0.8±0.5 pg/ml vs. 0.5±0.3 pg/ml, P=0.036). Positive correlations were found between IL-6 levels with BMI (ρ=0.519; P=0.001) and symptom severity (ρ=−0.556, P<0.001). In DCM compression model rats, IL-6 was elevated in CSF (40.5±3.3 vs. 13.2±2.4 pg/ml, P<0.001) and serum (7.1±1.7 vs. 2.9±1.6 pg/ml, P<0.001) samples from rats in the compression operation group compared with the sham operation group. Infusion of IL-6 in rats receiving the sham operation also led to motor function damage and mechanical allodynia threshold decline.ConclusionsSerum IL-6 level was elevated in DCM patients and its concentration can predict symptom severity. Local infusion of IL-6 led to myelopathy symptoms in model rats, which suggests that anti-inflammation can effectively treat DCM.

Is There Any Relationship between Plasma IL-6 and TNF-α Levels and Lumbar Disc Degeneration? A Retrospective Single-Center Study

“…Previous studies also have shown that IL-6 was significantly increased in intervertebral disc degeneration tissues and positively correlated with the degree of intervertebral disc degeneration and symptom severity. For example, Du et al [ 22 ] found that serum IL-6 levels were elevated during disc degeneration, and the concentration could predict the severity of symptoms. Our results also showed a statistically significant difference in serum IL-6 levels between the high-score group (total score > 18) and the low-score group (total score ≤ 18).…”

Do Inflammatory Cytokines Affect Patient Outcomes After ACDF?

“…18,19,37,38 In a rat myelopathy model, infusion of IL-6 resulted in motor dysfunction and mechanical allodynia threshold decline. 18 Likewise, IL-6 and IL-8 were shown to be elevated in the CSF of patients with myelopathy compared with control groups, scaling with the severity of spinal cord compression. 18,19,37,38 IL-6 concentrations have also been shown to be elevated in the serum of myelopathy patients.…”

“…18,19,37,38 IL-6 concentrations have also been shown to be elevated in the serum of myelopathy patients. 18 While the understanding of human cytokine profiles of patients with isolated radiculopathy is more limited, robust animal research studies have measured inflammatory markers in the setting of nerve root injury. 35,37,39,40 Recombinant TNF-α applied directly to the rat DRG, to mimic disc herniation, resulted in apoptosis of the DRG cellular nuclei.…”

“…Previous investigations have shown that increased IL-6 serum and discal expression is associated with increased myelopathy symptom severity as well as postoperative back pain and disability, respectively. 18,21 In a study of elderly women with acute lower back pain, plasma elevations of IL-6 were associated with depressive symptoms and pain while elevations of TNF-α were associated with disability and pain. 44 However, there is also evidence to suggest that IL-6 and TNF-α concentrations may not be significantly associated with pre-or postoperative outcomes as studies have demonstrated that preoperative functional status (Japanese Orthopaedic Association Scale) in myelopathy and VAS Back pain in degenerative disc disease did not correlate with patient serum and intradiscal IL-6 concentrations, respectively.…”

“…The cytokine expressions in patient discogenic tissue, CSF, and blood serum may not be comparable. 18,21,37 Inflammatory markers are associated with both local and systemic responses, where relative elevations in the serum may have been attenuated for local responses. 47 Moreover, the comparative profiles of patient cytokines have been demonstrated to vary significantly based on preoperative diagnosis, which may account for the discrepancy between our cohort and the positive findings in the literature.…”