Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical trials

The hunt for useful sepsis biomarkers is ongoing. Macrophage migration inhibitory factor (MIF) was implicated as a biomarker in sepsis, but its diagnostic and prognostic value has remained unclear in human studies. Here, we aimed at clarifying the value of MIF as a sepsis biomarker with the meta-analysis of clinical trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched until December 2019. From the included studies, blood MIF levels and indicators of disease severity were extracted in septic and control patient groups. Twenty-one eligible studies were identified, including data from 1876 subjects (of which 1206 had sepsis). In the septic patients, blood MIF levels were significantly higher than in healthy controls with a standardized mean difference (SMD) of 1.47 (95% confidence interval, CI: 0.96–1.97; p < 0.001) and also higher than in patient groups with nonseptic systemic inflammation (SMD = 0.94; CI: 0.51–1.38; p < 0.001). Markedly greater elevation in blood MIF level was found in the more severe forms of sepsis and in nonsurvivors than in less severe forms and in survivors with SMDs of 0.84 (CI: 0.45–1.24) and 0.75 (CI: 0.40–1.11), respectively (p < 0.001 for both). In conclusion, blood MIF level is more elevated in systemic inflammation caused by infection (i.e., sepsis) compared to noninfectious causes. In more severe forms of sepsis, including fatal outcome, MIF levels are higher than in less severe forms. These results suggest that MIF can be a valuable diagnostic and prognostic biomarker in sepsis given that well-designed clinical trials validate our findings.