Serial anti-tuberculous immune responses during the follow-up of patients with tuberculous pleurisy.

Little is known about the decay kinetics of interferon (IFN)-γ response and its influencing factors in tuberculous pleurisy. We enrolled thirty-two patients with tuberculous pleurisy prospectively and followed up at month 0, 6, and 9, at which time peripheral venous blood was drawn for interferon gamma release assay (IGRA) by means of QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic and clinical data were captured. To identify significant predictive factors influencing the IFN-γ response, multiple linear regression analyses were performed. Percentage of CD4+, CD8+, Vγ2Vδ2 T cells and Treg cells were measured by flow cytometry. The percentage of QFT-GIT-positive patients at baseline, month 6 and month 9 were 96.9% (30/32), 90.6% (29/32) and 84.4% (27/32), respectively. Quantitative IFN-γ response at baseline were significantly correlated with symptom duration (P = .003, R = 0.261) and age (P = .041, R = 0.132). Besides, the decreases of the IFN-γ response at month 6 and month 9 were positively correlated with the IFN-γ level at baseline. The dynamic tendency of the percentages of Treg cells was similar to the IFN-γ responses at each time-point. Quantitative IFN-γ response could be influenced by host immune status, instead of disease burden and anti-tuberculosis treatment. IGRA is probably not a useful biomarker of treatment efficacy in tuberculous pleurisy.

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

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.

Functional polymorphisms in the gene encoding macrophage migration inhibitory factor (MIF) are associated with active pulmonary tuberculosis.

OBJECTIVE: The role of the cytokine, macrophage migration inhibition factor (MIF) was assessed in tuberculosis. This case-control study investigated whether commonly occurring functional MIF polymorphisms are associated with active tuberculosis as well as with serum levels of MIF, IFN-γ and TNF-α. METHODS: Two MIF promoter polymorphisms, a functional -794 CATT5-8 microsatellite repeat (rs5844572) and a -173G/C single-nucleotide polymorphism (rs755622), were analysed by PCR and PCR-RFLP, respectively, in 47 patients and 50 healthy subjects. The mRNA level of MIF was performed by real-time PCR (RT-PCR), and MIF, IFN-γ and TNF-α serum levels were determined by ELISA. RESULTS: A significant increase of MIF mRNA expression and MIF protein level were found in patients compared to healthy controls. Meanwhile, the increase of IFN-γ and TNF-α serum levels were confirmed. According to the profile of genetic model, a significant association was found of genotypes carrying the -794 CATT 7 or 8 and -173 C risk alleles with susceptibility to active tuberculosis and with a significant increase of MIF, IFN-γ and TNF-α. CONCLUSIONS: These data suggested a distinct genetic and immunopathogenic basis for tuberculosis at the MIF locus. Serum MIF, IFN-γ and TNF-α profiles distinguish tuberculosis from the more inflammatory phenotype and may play a role in pathogenesis and as biomarkers of active tuberculosis.