Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit

Abstract

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum. The results indicated that serum levels of lymphocytes, plasma cells, granulocytes and monocytes were increased in patients with pulmonary tuberculosis in ICU compared with healthy controls. The serum levels of inflammatory factors interleukin (IL)-1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon-γ were detected in patients with pulmonary tuberculosis compared with healthy controls. It was demonstrated that high mobility group box-1 protein expression levels were higher in the serum of patients with pulmonary tuberculosis compared with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis caused by M. tuberculosis also upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that inflammatory responses and inflammatory factors are associated with the progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory responses and inflammatory factors may be beneficial for the treatment of patients with pulmonary tuberculosis in ICU.

Keywords: extracellular signal-regulated kinase/Akt; inflammatory factors; inflammatory responses; pulmonary tuberculosis.

Figure 1.

Changes in inflammatory cells in patients with MTB. The percentage of (A) lymphocytes, (B) plasmacytes, (C) neutrophils and (D) monocytes was analyzed in the serum of patients with MTB. The percentage of (E) macrophages, (F) mast cells and (G) endothelial cells was analyzed in the lung tissue of patients with MTB. (H) Expression levels of HMGB1 were analyzed in the lung tissue of patients with MTB. Data are expressed as the mean ± standard deviation of three independent experiments. Magnification, ×40. **P<0.01 vs. healthy controls. HMGB1, high mobility group box-1; MTB, Mycobacterium tuberculosis infection.

Figure 2.

Inflammatory factors in patients with MTB. Serum levels of (A) IL-1, (B) IL-6, (C) IL-10, (D) IL-12, (E) IL-2 and (F) IL-15 were analyzed in patients with MTB. Data are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 vs. healthy controls. IL, interleukin; MTB, Mycobacterium tuberculosis infection.

Figure 3.

Evaluation of Th1/Th2 cytokines in patients with MTB. Serum levels of (A) Th1 and (B) Th2 cells were evaluated in patients with MTB. (C) The balance of Th1/Th2 cytokines was analyzed in patients with MTB. Serum levels of (D) IL-4, (E) IL-17 and (F) IFN-γ were analyzed in patients with MTB. Data are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 vs. healthy controls. Th, T helper cell; IL, interleukin; IFN, interferon; MTB, Mycobacterium tuberculosis infection.

Figure 4.

Expression levels of TNF-α and MMPs in patients with MTB. Serum levels of (A) TNF-α, (B) MMP-1 and (C) MMP-9 were evaluated in patients with MTB. Protein expression levels of (D) TNF-α, (E) MMP-1 and (F) MMP-9 in human pleural mesothelial cells isolated from patients with MTB. Data are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 vs. healthy controls. TNF, tumor necrosis factor; MMP, matrix metalloproteinase; MTB, Mycobacterium tuberculosis infection.

Figure 5.

Analysis of TNF-α-induced ERK/ATK signaling pathway in hPMCs isolated from patients with MTB. Expression levels of (A) ERK and (B) Akt were evaluated in hPMCs isolated from patients with MTB. Phosphorylation levels of (C) ERK and (D) Akt in hPMCs isolated from patients with MTB. (E) Expression levels and (F) phosphorylation levels of ERK and Akt were evaluated in si-TNF-α-treated hPMCs. Expression levels of (G) MMP-1 and (H) MMP-9 were evaluated in si-TNF-α-treated hPMCs. Data are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 vs. healthy controls. TNF, tumor necrosis factor; MMP, matrix metalloproteinase; ERK, extracellular-signal-regulated kinase; hPMC, human pleural mesothelial cell; MTB, Mycobacterium tuberculosis infection; si, small interfering RNA.

Figure 5.

Analysis of TNF-α-induced ERK/ATK signaling pathway in hPMCs isolated from patients with MTB. Expression levels of (A) ERK and (B) Akt were evaluated in hPMCs isolated from patients with MTB. Phosphorylation levels of (C) ERK and (D) Akt in hPMCs isolated from patients with MTB. (E) Expression levels and (F) phosphorylation levels of ERK and Akt were evaluated in si-TNF-α-treated hPMCs. Expression levels of (G) MMP-1 and (H) MMP-9 were evaluated in si-TNF-α-treated hPMCs. Data are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 vs. healthy controls. TNF, tumor necrosis factor; MMP, matrix metalloproteinase; ERK, extracellular-signal-regulated kinase; hPMC, human pleural mesothelial cell; MTB, Mycobacterium tuberculosis infection; si, small interfering RNA.