Disc in flames: Roles of TNF-α and IL-1β in intervertebral disc degeneration

Abstract

The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc, incited by aging, traumatic insult, genetic predisposition, or other factors, is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, and compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes, exacerbated by cytokines TNF-α and IL-1β are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1β to changes seen during disc degeneration at the cellular and tissue level, new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

“…This model mimics human IVD degeneration, in which proinflammatory cytokines TNF-a and IL-1b are key mediators [5,38]. In this model, an up-regulation of pro-inflammatory markers (IL-6, IL-8, MMP1 and MMP3), as well as a down-regulation of ECM proteins (Col II and Agg) was observed [32], in accordance to findings reported during human disc degeneration [5,38].…”

Autophagy: A double-edged sword in intervertebral disk degeneration

“…MMPs and ADAMTSs are primary enzymes that are responsible for ECM degradation. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), both major pro-inflammatory cytokines, are highly expressed in degenerated IVD cells and tissues, and have been shown to increase the levels of MMPs and ADAMTSs [89,90]. In rat NP cells exposed to TNF-α or IL-1β, the expression of autophagy-related genes does not change; however, rapamycin (an autophagy activator) decreases the levels of MMP-3, MMP-9 and ADAMTS-4, and an opposite effect appears when treated with 3-MA (an autophagy inhibitor) [91].…”

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

“…In a porcine model, lumbar discs receiving exogenous TNF-α injection display degenerative changes with annulus fissure, cell cluster, NP matrix loss, vascularization, and interleukin (IL)-1β expression in the outer annulus, suggesting TNF-α as a driver in disc degeneration [16]. Moreover, inflammatory responses and ECM degradation elicited by TNF-α are considered as critical events in the process of IDD and associated LBP [17]. In this review, we summarize the expression patterns and roles of TNF-α in IDD and describe the recent progress regarding its inhibition as a promising biological therapeutic approach for disc degeneration.…”