Increased serum CXCL10 levels are associated with clinical severity and radiographic progression in patients with lumbar disc degeneration
Introduction
Lower back pain (LBP) afflicts approximately 70–80% of the global population at some point in their lives [1]. LBP is a significant contributor to patient morbidity and inflicts high long-term healthcare costs [2]. LBP often arises due to intervertebral disc degeneration (IDD) [3]. Despite the myriad of mechanisms, including nutrition, genetic, traumatic, and mechanical, that have been described in the degenerative process, a complete picture of how IDD develops is unclear [4], [5], [6]. IDD is typically treated with a mixture of conservative and operative approaches. Nevertheless, a large proportion of patients only manage to obtain limited degrees of symptomatic relief. Current treatment methods are unable to reverse IDD progression, with several patients remaining refractory to various therapeutic modalities [7]. Thus, a novel therapeutic target that may halt IDD development and progression is urgently needed.
Chemokines are a family of (8–12 kDa) heparin-binding messenger molecules that promote leukocyte migration [8]. Chemokines are structurally divided into 4 subfamilies: CXC, XC, CX3C, or CC [8]. Chemokines exert their biological activity by reacting with target cell surface G protein-linked transmembrane receptors [9]. Chemokines mediate several reactions such as mitogenesis, granulation, degranulation, apoptosis, organogenesis, angiogenesis, wound healing, and tissue homeostasis [10], [11], [12]. Both LDH and IDD have been found to involve chemokines in their respective disease processes. Studies have found raised systemic CCL5 and CXCL6 levels in moderate to severe LDD [13]. Elevated CX3CL1 expressions and CX3CR1-expressing cells are significantly associated with the occurrence of herniated nucleus pulposus [14]. Both CXCL12 and CCL3 are also involved in IDD progression [15], [16].
Monocytes and endothelial cells secrete C-X-C motif chemokine ligand 10 (CXCL10), also known as interferon-gamma induced protein 10 (IP-10), in retaliation to exposure to tumor necrosis factor-alpha (TNFα) and interferon-gamma (IFNγ) [17].CXCL10 exerts chemotactic effects on T lymphocytes and monocytes [18], leading to the activation of macrophages, dendritic cells, natural killer cells, as well as B and T lymphocytes [19], [20]. Various cells, especially the Th1 cell, express CXCR3, a CXCL10 receptor [21]. CXCL10/CXCR3 and its ligands are the cornerstones in the recruitment of inflammatory cells [22]. In inflamed tissues, recruited Th1 lymphocytes augment TNF-α and IFN-γ release, which go on to trigger a cascade of Th1-chemokines that serve to amplify the feedback loop[23]. Recent studies have indicated the potential role of CXCL10 in IDD development. One previous study showed that CXCL10 substantially enhances levels of annulus fibrosus cells [24]. The abundance of CXCRC in these recruited cells indicates that CXCL10 may be vital in repairing damaged annular cells [24]. Studies also demonstrated that CXCL10 is abundant in herniated disc tissue and may mediate inflammatory cell infiltration and spontaneous herniated tissue regression [25].
Interpreted as a whole, CXCL10 appears to have a key function in IDD progression. Nevertheless, there is a lack of research outlining the potential relationship between IDD disease severity and serum CXCL10 levels. We then sought to fill this knowledge gap by conducting the current study.
Section snippets
Study subjects
A total of 136 IDD patients with low back pain was enrolled between August 2020 to August 2021 for this study. Meanwhile, 127 gender- and age-matched asymptomatic volunteers and 120 healthy controls were also included. MRIs were used to diagnose IDD. All patients who presented with significant back pain were included in this study. Significant low back pain was defined as low back pain for 2 weeks that was severe enough to require medical consultation or treatment. Patients with a history of
Demographic data
Table 1 depicts clinicodemographic and laboratory data of included LBP patients. The IDD group consisted of 66 females (48.5%) and 70 males (51.5%), while the control group consisted of 60 females (47.2%) and 67 males (52.8%) and the healthy control group included 55(45.8%) females and 65 males(54.2%)(P = 0.513). The overall mean patient age was 44.29 years (range, 16–85 years), while the age of IDD patients, asymptomatic subjects and healthy controls were 45.6 ± 8.8, 46.1 ± 7.9 and 44.9 ± 8.8,
Discussion
LBP is a multifaceted and complex condition that involves a mixture of degenerative changes, environmental exposures, and hereditary predispositions [33]. IDD is a progressive and irreversible condition that is closely related to mechanical dysfunction of the affected segment. Therefore, there is an urgent need to seek a potential biomarker reflecting IDD disease progression.
The findings of our study demonstrate significantly elevated concentrations of serum CXCL10 in patients with symptomatic
CRediT authorship contribution statement
YJE and ZYC prepared and drafted the manuscript. ZKH, QY prepared the figures and tables. YJE and ZYC designed the study. YJE and QY collected data and conducted statistical analysis. ZKH performed ethical approval. All authors read and approved the final manuscript.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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