Role of Th1 and Th17 imbalance in acute lung injury mice
© Liu and Li; licensee BioMed Central Ltd. 2014
Published: 17 March 2014
Acute lung injury (ALI) is characterized by an excessive inflammatory response. Several recent clinical observations have shown that severe H1N1 influenza with ARDS is characterized by early secretion of Th17 (IL-6, IL-8, IL-9, IL-17) and Th1 (TNFγ, IL-15, IL-12p70) cytokines ,. However, the exact role of T-helper cells (Th) in the ALI model remains unknown. We hypothesized that there might be Th imbalance within the lung in the early phase of LPS-induced ALI. This study was to assess the role of lung Th polarization response in ALI mice.
C57BL/6 mice were randomly divided into two groups: control group and ALI group. ALI animals received 2 mg/kg LPS. Lung wet weight/body weight (LW/BW) was recorded to assess lung injury. The pathological changes were examined under an optical microscope. The mRNA expression levels of T-bet, GATA-3 and RORγt were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Meanwhile, levels of IL-6, IFNγ, IL-4 and IL-17 in lung homogenates were assessed by enzyme-linked immunosorbent assay.
The increase in LW/BW was induced in ALI mice. Histologically, widespread alveolar wall thickening caused by edema, severe hemorrhage in the interstitium and alveolus, and marked and diffuse interstitial infiltration with inflammatory cells were observed in the ALI group. Meanwhile, the levels of IL-6 in lung tissue were significantly enhanced in the LPS-induced ALI mice. The mRNA expression of T-bet and RORγt was upregulated in ALI mice at 24 hours and 48 hours relative to normal mice (P < 0.05 vs. Con). There was no significant difference in the expression of GATA-3 among groups at 24 hours and 48 hours. Meanwhile, the levels of IFNγ, IL-17 and IL-6 in lung tissue were significantly enhanced at 24 hours and 48 hours in the LPS-induced ALI mice. In addition, the levels of IL-4 in lung tissue were significantly enhanced at 48 hours in the LPS-induced ALI mice. The expression of T-bet mRNA and RORγt mRNA had a strong correlation with the IL-6 concentration. However, there was no significant correlation of GATA-3 with the IL-6 concentration. In addition, there was a significant correlation of IFNγ, IL-4 and IL-17 with the IL-6 level in LPS-induced ALI at 24 hours and 48 hours.
ALI provokes Th1 and Th17 polarization response. Th1 and Th17 may participate in the early inflammatory response to ALI.
Supported by the Research Project CPSFG 2013M542578, JSPSFG 1301005A, SYS201251 and 2013NJZS50.
This article is published under license to BioMed Central Ltd. This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2014 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2014. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.