Association between circulating cell-free mitochondrial DNA and inflammation factors in noninfectious diseases: A systematic review

Objective: This study aimed to assess the correlation between the circulating cell-free mitochondria DNA and inflammation factors in noninfectious disease by meta-analysis of data from eligible studies.

Materials and methods: Through a comprehensive searching of pubmed, embase, web of science, cochrane from establishment of the database to October 31, 2022, studies were selected that investigated the association of circulating cell free mitochondria DNA with inflammatory factors in non-infectious diseases. Studies that met the inclusion criteria and were published in English or Chinese were included. Data of each correlation coefficients were extracted from the paper and 95% confidence intervals were calculated. Sensitivity and heterogeneity tests were carried out for each data.

Results: A total of 660 articles were retrieved and 22 were included in this meta-analysis, including 2600 patients. A fixed effects model was employed to examine ISS and IL-8, others were analyzed using random effects models. The correlation coefficient between mtDNA and ISS score was 0.37 (95%CI = [0.232;0.494]), p<0.0001, heterogeneity I2 = 46%, p = 0.11). The correlation coefficients between mtDNA and inflammatory factors are as follows: TNFα, 0.405 [(95%CI = [0.253;0.538], p<0.0001, heterogeneity I2 = 77%, p = 0.0001]. IL-6, 0.469 [(95%CI = [0.296;0.612]), p = 0.0001, heterogeneity I2 = 93%, p<0.0001]. CRP, 0.333[(95%CI = [0.149;0.494]), p = 0.005, heterogeneity I2 = 85%, p<0.0001]. IL-8, 0.343[(95%CI = [0.233;0.524]), p = 0.001, heterogeneity I2 = 50%, p = 0.09]. PCT, 0.333 [(95%CI = [0.06;0.64]), p = 0.09,heterogeneity I2 = 64%,p = 0.06]. There were no significant publication bias for TNFα, IL-6 and CRP.

Conslusion: Circulating cell free mtDNA was moderate positively correlated with the expression of inflammatory factors and the degree of trauma.