Lower Plasma Melatonin in the Intervertebral Disk Degeneration Patients Was Associated with Increased Proinflammatory Cytokines

Abstract

Background: Intervertebral disc degeneration (IDD) was considered to be the pathological basis of intervertebral disc herniation (IDH). However, the plasma melatonin in the IDD cases and healthy controls remained unclear.

Methods: In this case-control study, a total of 71 IDD cases and 54 healthy controls were enrolled between April 2020 and August 2020. The diagnostic effect of plasma melatonin for IDD was detected using receiver operating characteristic curve. The correlations between two continuous variables were detected with the Pearson linear analyses.

Results: It was found that lower melatonin concentration was detected in the IDD cases (1.906 ± 1.041 vs 3.072 ± 0.511 pg/mL, P<0.001). Through receiver operating characteristic curve analyses, it was found that plasma melatonin could be used as a diagnostic biomarker for IDD (area under curve=0.808, P<0.001). In advanced correlation analyses, it was found that plasma melatonin concentration was negatively associated with the age, symptom durations, IDD disease severity and proinflammatory factors, including IL-6 and TNF-α concentrations (P<0.05). Comparing with the higher melatonin groups, significantly increased IL-6 (0.601 ± 0.085 vs 0.507 ± 0.167 pg/mL, P=0.028) and TNF-α (3.022 ± 0.286 vs 2.353 ± 0.641, P<0.001) were detected in the patients with lower melatonin concentration.

Conclusion: The plasma melatonin concentration was significantly decreased in the IDD cases and plasma melatonin could be used as a diagnostic biomarker for IDD. Lower plasma melatonin was associated with longer disease durations, elevated disease severity and higher inflammatory cytokines levels in IDD patients.

Keywords: biomarker; inflammatory factors; intervertebral disc degeneration; melatonin.

Figure 1

The flow chart of participants screening, including, grouping, examination and analyses in this study.

Figure 2

Decreased plasma melatonin in IDD cases. (A) A significantly decreased plasma melatonin was detected in the IDD cases in stage 3, 4 and 5. **P<0.01, ***P<0.001. (B) melatonin could be used as a diagnostic biomarker for IDD with an area under curve of 0.808 and P<0.001.

Figure 3

The correlation matrix of the plasma melatonin, clinical characteristic and experiment examinations. (A) The correlation matrix of the plasma melatonin, clinical characteristic and experiment examinations in healthy controls. (B) The correlation matrix of the plasma melatonin, clinical characteristic and experiment examinations in healthy controls. The circle size reflected the Pearson r value. Most red reflected −1 while most blue reflected 1 in the figures.

Figure 4

The associations between melatonin and proinflammatory factors. (A) No significant linear association between melatonin and IL-1β level in the IDD cases (R²=0.032, P=0.137). (B) Negative linear correlations between plasma melatonin and IL-6 (R²=0.407, P<0.001). (C) Negative linear correlations between plasma melatonin and TNF-α (R²=0.575, P<0.001). All the analyses were detected using a linear regression analyses model.

Figure 5

Increased plasma pro-inflammatory factors in the IDD cases. The severity of the IDD cases were determined using the Pfirrmann grade (Grades 2–5). There were 7, 10, 28 and 26 IDD cases in the Pfirrmann grade 2, 3.4 and 5 group. Respectively. (A) The plasma IL-1β between control subjects and IDD cases in different stages. (B) The plasma IL-6 between control subjects and IDD cases in different stages. (C) The plasma TNF-α between control subjects and IDD cases in different stages. *P < 0.05, **P < 0.01, and ***P<0.001.