The Effects And Mechanisms Of Lipo-prostaglandin E₁ On Mice Lipopolysaccharide Induced Acute Lung Injury

Acute lung injury (ALI) is a common severe disease. The mortality is very high, and it seriously threatens the lives of severe patients and their living quality. In our country, although intensive care medicine has a great development, it's not optimistic to the cognition and therapy condition of ALI. At present, there is no effective drug therapeutic regimen. Therefore, early diagnosis and effective control are critical to the treatment of ALI and acute respiratory distress syndrome (ARDS). This will be great helpful to the work of medical personnel in respiration and intensive care medicine.In the process of ALI, cascade amplification of the inflammatory plays a key role. Now research on multiple mediators of inflammation has revealed that normal lung is in a refined balance of inflammation and anti-inflammation. The two phenotypes of helper T cell just deputy above-mentioned balance. It has been shown that there is unbalance of the Th1/Th2 in ALI, excursion from Th1 to Th2. Detecting the level of cytokine can reflect the balanced condition of Th1/Th2. However, in departed researches, the function of the T cell was mostly studied in vitro, which could not veritably reflect the actual function of the T cell. In our research, we adopt flow cytometry to detect and reflect the function of the T cell precisely at single cell level after in vivo stimulus. So aiming directly at immune hypofunction, choosing proper juncture and effective immunological regulation measure to recover the balance of inflammation and anti-inflammation, may be an important direction for prevention and treatment of ALI.Objectives: To probe the effect of lipo-prostaglandin E₁ (PGE₁) on lipopolysaccharide (LPS) induced ALI and to investigate the underlying mechanisms. Methods: ALI was induced in BALB/c mice by intravenous injection of LPS. PGE₁ or dexamethasone was administered 1 hour after LPS deliver. After 6 hours of LPS deliver, lung wet-to-dry ratio and lung morphology were studied. The expression of CD4, Th1 and Th2 phenotype cytokines was detected by flow cytometry. Interferon-γ(IFN-γ) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were measured by ELISA.Results:1. PGE₁ and dexamethasone significantly reduced the lung hemorrhage, edema, exudation and neutrophil infiltration. In addition, PGE₁ and dexamethasone significantly attenuated the lung wet-to-dry weight ratio.2. Compared with the control group, Th, Th1 and Th2 cells were markedly decreased in LPS group. Both PGE₁ and dexamethasone treatment markedly increased Th cells. Contrary to further decreased Th1 and Th2 cells by dexamethasone treatment, PGE₁ treatment increased them but not significantly.3. Compared with the control group, Th1/Th2 was markedly decreased in LPS group. Compared with the LPS group, Th1/Th2 was decreased by dexamethasone treatment.4. Compared with the control group, IFN-γlevel in BALF was markedly decreased in LPS group while being increased with PGE₁ treatment. Compared with the control group, IL-6 level in BALF was significantly increased in LPS group. Both PGE₁ and dexamethasone treatment decreased it, but only significantly in dexamethasone treated group.Conclusions:1. Excursion of Th cell in LPS-induced ALI is at low level, Th1 to Th2.2. Glucocorticoid and lipo-prostaglandin E₁ can affect on excursion of Th cells, improve ALI. Targeting excursion of Th1 to Th2 cells, PGE₁ may represent a promising strategy to attenuate LPS-induced ALI.