Clinical Biomarker of Sterile Inflammation, HMGB1, in Patients with Chronic Non-Specific Low Back Pain: A Pilot Cross-Sectional Study

Abstract

The present study explores whether the inflammatory biomarker of sterile inflammation, high mobility box 1 (HMGB1), contributes to the inflammatory/nociceptive pathophysiology that characterizes chronic non-specific low back pain (LBP). Patients with chronic LBP (N = 10, >3 pain score on a 11-point Visual Analogue Scale, VAS) and asymptomatic participants (N = 12) provided peripheral blood (PB) samples. The proportion of classical CD14++ monocytes within PB leukocytes was determined by flow cytometry. The plasma and extracellular HMGB1 levels in unstimulated adherent cell (AC) cultures were measured using specific immunoassays. HMGB1 localization in ACs was assessed by immunofluorescent staining. The relative gene expression levels of tumor necrosis factor α (TNFα), interleukin-1 beta (IL-1β) and HMGB1 were determined by quantitative polymerase chain reaction (qRT-PCR) in relation to the pain intensity (11-point VAS scores) in patients with LBP. The extracellular release of HMGB1 in the LBP patient AC cultures was significantly elevated (p = 0.001) and accompanied by its relocation into the cytoplasm from the nuclei. The number of CD14++ monocytes in the patients’ PB was significantly (p = 0.03) reduced, while the HMGB1 plasma levels remained comparable to those of the controls. The mRNA levels of TNFα, IL-1β and HMGB1 were overexpressed relative to the controls and those of HMGB1 and IL-1β were correlated with the VAS scores at a significant level (p = 0.01–0.03). The results suggest that HMGB1 may play an important role in the pathophysiology of chronic non-specific LBP.