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

Abstract

BackgroundMacrophage 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.MethodsThe 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.ResultsMIF 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).ConclusionsA 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.

Prognostic value of serum macrophage migration inhibitory factor levels in pulmonary tuberculosis

“…In this study, we found that MIF level was significantly decreased ( P < 0.01) in 0, 3 and 6 months after treatment, then it entered into a plateau in 9 to 12 months. Similarly, another study reported decreased MIF levels in 2, 4, and 6 months after treatment ( P < 0.01) [14]. Kuai et al [15] found that TB could be distinguished from other inflammatory phenotype with profiles of serum MIF, IFN-γ and TNF-α, which might make effects in pathogenesis and be available as indicators of active tuberculosis.…”

“…MTB infection was hard to be inhibited since the proinflammatory response could be generally suppressed with the excessive generation of anti-inflammatory cytokines [23]. MIF was a critical cytokine responsible for the innate immunity and inflammatory responses, which was reported to make critical effects in both PTB development [24] and severity [14]. Until now, our study has been the first report to measure serum levels of MIF in PTB and further assess its association with the 12-month prognosis.…”

“…It proposed that MIF could induce the production of TNF-α and other pro-inflammatory cytokines [12, 13]. Furthermore, serum levels of MIF were reported to be a useful marker for assessing the effects of therapy in active pulmonary tuberculosis (APTB) patients [14]. Another study suggested a distinct genetic and immunopathogenic basis for TB at the MIF locus and serum MIF, IFN-γ and TNF-α profiles distinguish TB from the more inflammatory phenotype, as well as making effects in pathogenesis and as biomarkers of active TB [15].…”

Biomarcadores da tuberculose: uma revisão da literatura.

“…Em contrapartida houve um achado particular, citando que há divergência nos resultados dos marcadores e deles para com a sua comparabilidade. Shang et al (2018) investigaram o papel da citocina Fator de Inibição da migração de Macrófagos (MIF) associada ao Fator de Necrose Tumoral α (TNF-α) e IFN-γ no curso da quimioterapia em pacientes chineses hospitalizados. Já no período de pré-tratamento os 47 participantes foram dicotomizados em níveis altos (39) e baixos (8) de MIF, com níveis altos desta sendo relacionados ao TNF-α.…”

“…A respeito das doenças de base listadas nos pacientes do estudo, haviam indivíduos com câncer, diabetes, hepatites B e C e fumantes com história pregressa. Os autores não refletem as repercussões desses quadros na dinâmica dos biomarcadores pesquisados, o que dificulta maiores conclusões (SHANG et al, 2018).…”