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Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical
Janos Toldi1,2, David Nemeth3, Peter Hegyi3
1Department of Thermophysiology, Institute for Translational Medicine, Medical School, University of Pecs, Pecs, Hungary.
Abstract:
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.
Insights
Macrophage migration inhibitory factor (MIF) shows higher blood levels in sepsis patients compared to healthy individuals and those with non-septic inflammation. Elevated MIF levels indicate more severe sepsis and poorer outcomes, suggesting its potential as a sepsis biomarker.
Area of Science:
- Biochemistry
- Immunology
- Clinical Medicine
Background:
- Sepsis biomarker discovery is crucial for early diagnosis and prognosis.
- Macrophage migration inhibitory factor (MIF) has been proposed as a potential sepsis biomarker.
- Previous human studies on MIF's diagnostic and prognostic value in sepsis remain inconclusive.
Purpose of the Study:
- To clarify the diagnostic and prognostic value of Macrophage Migration Inhibitory Factor (MIF) as a sepsis biomarker.
- To conduct a meta-analysis of clinical trials investigating MIF levels in sepsis patients.
Main Methods:
- Systematic literature search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases until December 2019.
- Extraction of blood MIF levels and disease severity indicators from eligible studies.
- Meta-analysis of data from 21 studies involving 1876 subjects (1206 with sepsis).
Main Results:
- Blood MIF levels were significantly higher in sepsis patients compared to healthy controls (SMD: 1.47) and non-septic systemic inflammation (SMD: 0.94).
- Higher MIF levels were observed in severe sepsis and non-survivors compared to less severe forms and survivors (SMD: 0.84 and 0.75, respectively).
- All comparisons showed statistically significant differences (p < 0.001).
Conclusions:
- Blood MIF levels are elevated in sepsis, distinguishing it from non-infectious inflammatory conditions.
- Increased MIF levels correlate with sepsis severity and predict poorer outcomes, including mortality.
- MIF shows promise as a valuable diagnostic and prognostic biomarker for sepsis, pending validation through further clinical trials.
