The contradictory effect of macrophage-related cytokine expression in lumbar disc herniations: a systematic review

Abstract

Purpose Sciatic symptoms due to lumbar disc herniation are likely to be caused not solely by mechanical compression of the nerve root, but also by pain-inducing elements from inflammatory processes. Key components in the inflammatory reaction are M1 and M2 macrophages, with the M1 type being associated with pro-inflammatory processes and M2 with anti-inflammatory-processes. Method The present systematic review summarizes all studies on associations between M1 and M2 macrophages and their related inflammation factors and pain symptoms in lumbar disc herniations. Literature search was performed using an optimally sensitive search string. Studies were selected for inclusion by means of predefined inclusion and exclusion criteria and subsequently graded for risk of bias. A total of 14 studies were included. Overall risk of bias was moderate (8/14), and three studies had high risk of bias and three has low risk of bias. Results Regarding M1-related cytokines, high levels of TNF-α, TNFR1, IL-6, IL-8, and IFN-γ were all associated high VAS scores. In contrast, high levels of TNFR2 were associated with lower VAS scores. Moreover, no associations were found for IL-1a and IL-1β. Results regarding M2-related cytokines revealed the opposite: high levels of both IL-4 and IL-10 were associated with lower VAS scores. No associations were established for TGF-β. Moreover, the presence of macrophages (CD68) was negatively associated with VAS scores. Conclusion While M1-related pro-inflammatory cytokines worsen pain symptoms, M2-related anti-inflammatory cytokines alleviate pain symptoms. Nevertheless, the present evidence is limited, and further research on the underlying pathophysiological mechanism in sciatica is required.

Ozone as Modulator of Resorption and Inflammatory Response in Extruded Nucleus Pulposus Herniation. Revising Concepts

“…M2 is believed to alleviate pain symptoms through resorption of herniated disc material. During most inflammation processes, M1 or M2 macrophages occur sequentially [31][32][33][34]. Cytokines excreted during the process of disc herniation in sciatica seem to have a different effect on pain symptoms.…”

“…Cytokines excreted during the process of disc herniation in sciatica seem to have a different effect on pain symptoms. Pro-inflammatory cytokines worsen pain symptoms, while anti-inflammatory cytokines alleviate pain symptoms [34] (Figure 1).…”

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

“…( 17)IL-1 is produced by monocytes and macrophages in the form of a proprotein, which is proteolytically processed and released in response to cell injury, thus inducing apoptosis [32]. Moreover, the IL1A gene has been previously identified to carry a threefold risk of disc bulges compared to controls [9,33]. It has been shown that an increased level of the pro-inflammatory IL1A antagonizes IL-1 receptor antagonist (IL1RN) in the degenerated disc as there is a dysregulation about tissue destruction [27].…”

TNF-ɑ Induces Methylglyoxal Accumulation in Lumbar Herniated Disc of Patients With Radicular Pain

“…It is caused not solely by mechanical compression of the nerve root but also by the release of many inflammatory molecules ( Takahashi et al, 1996 ; Ahn et al, 2002 ; Scuderi et al, 2006 ; Pedersen et al, 2015 ). Clinical data indicate that 20–76% of nerve root compression due to a disc herniation is painless, and some cases with slight disc herniation suffer severe pain ( Takada et al, 2001 ; Djuric et al, 2020 ). Therefore, a chemical factor may play an important role in radicular leg pain, following lumbar disc herniation ( Andrade et al, 2013 ; Hasvik et al, 2019 ; Wang et al, 2020 ).…”