Ann Lab Med.  2018 Jan;38(1):9-16. 10.3343/alm.2018.38.1.9.

Serum Macrophage Migration Inhibitory Factor as a Biomarker of Active Pulmonary Tuberculosis

• Shang ZB
• Wang J
• Kuai SG
• Zhang YY
• Ou QF
• Pei H
• Huang LH

• KMID: 2397596
• DOI: http://doi.org/10.3343/alm.2018.38.1.9

Abstract

BACKGROUND
Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine with chemokine-like functions, has been shown to play a central role in several acute and chronic inflammatory diseases. However, limited information is available regarding the use of MIF as an inflammatory pathway marker in patients with tuberculosis. This study aimed to investigate the association of MIF with IFN-γ and TNF-α in active pulmonary tuberculosis (APTB) following anti-tuberculosis treatment.
METHODS
The MIF, TNF-α, and IFN-γ serum levels were determined in 47 patients with APTB by cytokine-specific ELISA at four phases: prior to anti-tuberculosis drug treatment (baseline), and following 2, 4, and 6 months of treatment. In addition, we measured the MIF, TNF-α, and IFN-γ serum levels in 50 health controls.
RESULTS
MIF serum levels were significantly elevated (P < 0.05) in patients with APTB prior to treatment compared with that in control subjects, and TNF-α≥449.7 pg/mL was associated with high MIF levels (≥13.1 ng/mL). MIF levels were significantly reduced (P < 0.01) following 2, 4, and 6 months of treatment, with variations in TNF-α and IFN-γ serum levels. MIF levels were positively correlated with the paired TNF-α level at baseline (r=0.1103, P=0.0316) and following 6 months of treatment (r=0.09569, P=0.0364).
CONCLUSIONS
A reduction in the MIF serum levels in patients with APTB following anti-tuberculosis treatment may positively affect host immune protection against Mycobacterium tuberculosis infection. Thus, serum MIF levels may constitute a useful marker for assessing therapy effectiveness in patients with APTB.

Keyword

Macrophage migration inhibitory factor; TNF-α; IFN-γ; Active pulmonary tuberculosis

MeSH Terms

Enzyme-Linked Immunosorbent Assay
Humans
Macrophages*
Mycobacterium tuberculosis
Tuberculosis
Tuberculosis, Pulmonary*

Figure

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  Fig. 1 Serum levels of MIF, TNF-α, and IFN-γ in 47 patients with active pulmonary TB and 50 control subjects. (A) MIF levels in patients with TB (17.19 ng/mL [12.71–21.67] and in control subjects (9.36 ng/mL [7.29–11.43]. (B) TNF-α levels in patients with TB (583.6 pg/mL [453.1–844.5] and in control subjects (343.3 pg/mL [298.6–434.2]. (C) IFN-γ levels in patients with TB (559.5 pg/mL [255.0–864.0] and in control subjects (396.7 pg/mL [189.5–603.9]. Data are presented as median values (interquartile range).Abbreviation: MIF, macrophage migration inhibitory factor.

• 

  Fig. 2 Serum levels of inflammatory cytokines (MIF, TNF-α, and IFN-γ) in active pulmonary tuberculosis (APTB). Patients with APTB (n= 47) at baseline and following 2, 4, and 6 months of anti-tuberculosis drug (ATD) treatment are indicated with solid lines. Serum levels of inflammatory cytokines in healthy controls at baseline (n=50) are shown with dotted lines. (A) The MIF level in patients with APTB was 17.19 (12.71–21.67) ng/mL at baseline and decreased to 14.57 (11.98–16.98) ng/mL, 9.79 (8.17–12.35) ng/mL, and 7.84 (6.34–8.70) ng/mL following 2, 4, and 6 months of ATD therapy, respectively. (B) The TNF-α level in patients with APTB was 583.6 (453.1–844.5) pg/mL at baseline and decreased to 481.6 (398.7–504.0) pg/mL, 415.5 (346.7–454.9) pg/mL, and 374.5 (312.0–415.0) pg/mL following 2, 4, and 6 months of ATD therapy, respectively. (C) The IFN-γ level in patients with APTB was 559.5 (255.0–864.0) pg/mL at baseline and decreased to 535.2 (341.2–794.0) pg/mL, 465.7 (258.3–649.9) pg/mL, and 401.2 (227.2–574.6) pg/mL following 2, 4, and 6 months of ATD therapy, respectively. Data are presented as median values (interquartile range); error bars indicate standard error of means.Abbreviation: MIF, macrophage migration inhibitory factor.

• 

  Fig. 3 Relationship between serum MIF levels and TNF-α and IFN-γ levels. Levels at baseline (A) and following 2 months (B), 4 months (C), and 6 months (D) of ATD therapy. Only the inflammatory cytokines MIF and TNF-α exhibited a statistically significant (P<0.05) Spearman correlation coefficient value in patients with APTB at baseline and following 6 months of ATD treatment (A and D).Abbreviation: MIF, macrophage migration inhibitory factor.

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