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. Graphic abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.]