Bronchoalveolar Lavage Fluid Levels Of TNF-α Research Articles

Effects of epinephrine on early inflammatory cytokines and acute lung injury in endotoxemic rats

Objective To investigate the effects of epinephrine in sepsis-associated lung injury in rats. Methods Thirty SD rats were randomly divided into three groups(n=10 per group): control group received intravenous 0.9% saline 2.4 ml/(kg·h); LPS group received intravenous LPS(6 mg/kg); epinephrine treatment group received an infusion of epinephrine 0.6 μg/(kg·min) after LPS intravenous injection.Blood samples were taken at 2 h and 6 h after LPS injection and the levels of serum tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-10 were detected.The rats were sacrificed at 6 h. The lung tissues and bronchoalveolar lavage fluid(BALF) were collected.Pathological changes of the lung tissues were observed under light microscope.Water content of lung, expression of TNF-α, IL-6 and IL-10 in BALF and in serum were detected. Results (1)The water content of lung in LPS group significantly increased compared with that in control group(85.24%±5.87% vs. 70.19%±5.87%)and epinephrine group(78.00%±6.41%)(P<0.05). (2)Pathological examination showed that LPS could cause pulmonary capillary hyperemia, edema, inflammatory cells infiltration.Atelectasis and alveolar edema were found in small number of lung tissue.Compared with LPS group, epinephrine ameliorated the lung pathological injury.(3)Compared with LPS group, serum levels of TNF-α and IL-6 significantly decreased(P<0.05), whereas IL-10 increased(P<0.05) in epinephrine group.(4)Compared with LPS group, BALF levels of TNF-α[(78±9)ng/L vs.(102±16) ng/L] and IL-6[(268±42)ng/L vs.(347±50) ng/L]significantly depressed(P<0.05), whereas BALF levels of IL-10[(210±23)ng/L vs.(146±34) ng/L]elevated(P<0.05) in epinephrine group. Conclusion Epinephrine could reduce the acute lung injury caused by LPS.Its protective effect may be related to decreasing the levels of TNF-α and IL-6, elevating IL-10 level. Key words: Epinephrine; Sepsis; Inflammatory mediators; Acute lung injury; Rats

Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Rhodiola rosea L. (RRL) possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF) rat model. Lung fibrotic injury was induced in Sprague–Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg). The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH) and total superoxide dismutase (T-SOD), as well as lung tissue hydroxyproline (HYP) content. Tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01) and increased GSH and T-SOD contents. BALF levels of TNF-α, TGF-β1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9) and α-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-β1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may play important roles in BLM-induced PF.

Effect of inhaled toluene diisocyanate on local immune response based on murine model for occupational asthma

Highly reactive, low-molecular-weight diisocyanates (DIC) are the most commonly identified cause of occupational asthma (OA). Animal/clinical studies of DIC asthma have been more limited compared with atopic asthma, and an understanding of DIC pathogenesis is less clear. The aim of this study was to investigate in a mouse model, toluene diisocyanate (TDI, as 2,4-TDI isomer)-induced inflammatory reactions/cytokine profile changes in the lungs and accompanying changes in lymph node lymphocyte sub-populations. The study used female BALB/cJ/Han/IMP mice that were exposed first intra-nasally and then in an inhalation chamber to TDI or air. After the final exposure, bronchoalveolar lavage fluid (BALF) was collected and changes induced in inflammatory cell composition, levels of key cytokines (i.e. IL-4, TNFα, IFNγ), and lymphocyte sub-population profiles within auricular lymph nodes, were evaluated. Total number of cells in the BALF of treated mice was significantly higher than in control mice BALF. There was also a significant increase in BALF neutrophil and eosinophil levels with TDI mice compared to in controls; lymphocyte and macrophage numbers did not significantly differ. A significant increase in BALF levels of TNFα and IFNγ was also noted in mice exposed to TDI relative to levels in controls. BALF IL-4 levels were also increased, but the change from control was not significant. Lastly, the levels/percentages of CD3+CD4+ (T-helper [TH]) lymphocytes significantly increased in the lymph nodes of TDI-exposed groups while those of the CD3+CD8+ cells decreased as compared to in control mice. These studies, the first to assess TDI-induced changes in levels of three key cytokines in BALF in conjunction with changes in local lymph nodes following first an intra-nasal and then a general inhalation exposure to a low-level of TDI, confirm that TDI inhalation induces a pathology manifested by airway inflammation, TH cell-derived cytokine production, and shifts in lymph node lymphocytes sub-populations toward increases in TH cells.