Exploring causal correlations between blood inflammatory cytokines and low back pain: a Mendelian randomization

Abstract Purpose Low back pain (LBP) is a common and recurring public health problem that affects sufferers both physically and mentally and warrants further research. A succession of studies have suggested a plausible role for inflammatory cytokines in the pathogenesis of LBP. To date, there is no conclusive mechanism explaining how inflammatory cytokines affects LBP. Methods A bidirectional two-sample Mendelian randomization (MR) investigation was undertaken in two stages. The initial phase encompassed 41 inflammatory cytokines as the exposure, with LBP as the outcome, and the subsequent phase adopted the inverse approach. A total of 41 blood inflammatory cytokines were extracted from the genome-wide association study meta-analysis database, encompassing 8,293 individuals. Data pertaining to LBP were acquired from the Finnish biobank. Primary findings were computed using inverse-variance weighting (IVW), while sensitivity analyses accounting for pleiotropy and invalid instruments were conducted utilizing the weighted-median estimator, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier. Results Our results suggest that higher levels of Macrophage migration inhibitory factor (MIF) as well as lower levels of C-C motif chemokine ligand 3 (CCL3) are associated with an increased risk of LBP (odds ratio OR = 1.134, 95% confidence interval CI = 1.032–1.245, P = 0.009; OR = 0.887, 95% CI = 0.803–0.980, P = 0.018). Moreover, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. In contrast, in studies of the effect of LBP on inflammatory cytokines, genetically determined LBP had no causal effect on 41 inflammatory cytokines (IVW P > 0.05). Conclusions Our study confirms that the levels of circulating MIF and CCL3 may be regarded as valuable circulating inflammatory biomarkers for the management of LBP in clinical practice and as potential molecules for future mechanistic investigation and drug target identification.