ObjectiveTo investigate the expressions of IL-10,tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in serum and lung tissue of COPD rats in order to elucidate the potential mechanism of airway inflammation. MethodsForty-five healthy adult male SD rats were randomly divided into a COPD model group (n=30) and a normal control group (n=15). The COPD rat model was established by intratracheal instillation of lipopolysaccharide (LPS) and exposure to cigarette smoke for 28 days. The concentrations of IL-10,TNF-α and IFN-γ in serum and lung tissue were measured by ELISA. ResultsTNF-α level of serum and lung tissue in the COPD model group increased significantly compared with the control group(P<0.05),while the levels of IFN-γ and IL-10 decreased significantly[serum:(44.68±8.67) ng/L vs. (75.96±10.59) ng/L;lung tissue:(64.55±9.03) ng/L vs. (94.06±8.71) ng/L,P<0.01]. The level of IL-10 in serum and lung tissue was negatively correlated with TNF-α (serum:r=-0.67,lung tissue:r=-0.80,P<0.01). The level of IL-10 in serum and lung tissue was positively correlated with IFN-γ (serum:r=0.64,lung tissue:r=0.72,P<0.01). The level of IL-10 in serum and lung tissue was negatively correlated with the percentage of neutrophils(serum:r=-0.70,lung tissue:r=-0.67,P<0.01). ConclusionIn COPD rats,down regulation of IL-10 plays an important role in regulation of airway inflammation.
Objective To investigate the role of IFN-γ in suppressing bleomycin-induced pulmonary fibrosis in rats.Methods Seventy-five SD rats were randomly divided into five groups (15 rats in each group)，ie.a normal group，a bleomycin-induced pulmonary fibrosis model group，a dexamethasone-treated group，a high-dose IFN-γ-treated group (150 000 U/kg) and a low-dose IFN-γ-treated group (50 000 U/kg).Five rats in each group were randomly killed in 7th day，14th day and 28th day after relative treatment respectively，and lung tissue samples were harvested for histopathology study.HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.Histoimmunochemical method were adapted to determine protein levels of TGF-β1，CTGF，type Ⅰcollagen and type Ⅲ collagen in pulmonary tissues.Results Histopathological study showed that treatment with either dexamethasone or IFN-γ (both high dose and low dose) remarkably meliorated the extent of alveolus inflammation and suppressed pulmonary fibrosis (compared with model group，all Plt;0.05).Histoimmunochemical study suggested that both dexamethasone and IFN-γ could inhibit the expression of TGF-β1，CTGF，type Ⅰand type Ⅲ collagen (compared with model group，all Plt;0.05)，and the suppression of TGF-β1，type Ⅰand type Ⅲ collagen expression was more obvious in high-dose IFN-γ-treated group than those in low-dose group (Plt;0.05).Conclusions INF-γ possesses apparent anti-fibrosis effect that is similar to dexamethasone but with less side effect.Such effect may resulted from reduced production of type Ⅰand type Ⅲ collagen through expression inhibition of cytokines such as TGF-β1 and CTGF.
Objective To explore the immunopathologic mechanism underlying the inflammatory response after severe acute respiratory syndrome（SARS） invasion.Methods Pathway focused cDNA microarrays were employed for comparision of the gene expression patterns in 16HBEs treated with interferon-γ(IFN-γ) or the S protein of SARS-CoV.The S proteins were administered to BALB/c mice and the pathological changes of lung and spleen were observed.Results S protein activated JAK/STAT signal pathway in the 16HBEs with inducible protein 10（IP-10） gene expression，and the specific inhibitors of the JAK/STAT signal pathway were able to downregulate the induction of IP-10.The mice instilled intracheally with S proteins revealed obvious acute diffuse damage and increased IP-10 expression and CD68+ macrophages infiltration in both lung and spleen tissues.In contrast，the treatment with JAK3 inhibitors attenuated lung and spleen injury in the mice.Conclusion Our findings support that the activation of JAK/STAT pathway induced by SARS-CoV S protein plays a key role in promotion of an IFN -γ inducible chemokine cascade，which can help in the development of novel drug and therapeutics for prevention and treatment of SARS.
Objective To investigate the expression of aquaporin-1( AQP-1) in pulmonary tissues of asthma mice and the effects of acetazolamide( AZ) on AQP-1 expression. Methods Forty C57BL/6 mice were randomly divided into five groups. Group A was treated with phosphate buffer as a non-asthmatic group.The mice in group B, C, D, and E were sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The mice in group B, C, and D were interperitoneally injected with AZ at doses of 300, 200, 100 mg/kg, respectively during the challenge period. Results ①Wet/dry weight ratio of lung tissues in group E was significantly higher than that in group A( P lt;0. 05) , while it was lower in B, C and D groups than group E. ②The total number of cells, the number of eosinophils, and interleukin-5( IL-5) inBALF of group E were higher than those in group A( P lt;0. 05) , and interferon-γ( IFN-γ) level was lower in group E than in group A ( P lt; 0. 05) . After AZ treatment, the total number of cells, the number of eosinophils, neutrophils and lymphocytes were significantly decreased( P lt; 0. 05) , which were positively correlated with the dose of AZ. ③AQP-1 were expressed in tracheal epithelium, microvascular endothelial cell and bronchial peripheral vascular bed, and the expression in group E was significantly higher than that in group A( P lt;0. 01) . AQP-1 expression was significantly decreased after the intervention of AZ ( P lt;0. 05) .The decrease was positively correlated with the dose of AZ. The expression of AQP-1 mRNA showed no significant difference among these groups( P gt;0. 05) . Conclusions AQP-1 was over-expressed in the lung tissue of mice with asthma. AZ can inhibit the expression of AQP-1 and relieve lung inflammatory cells infiltrationin a dose-dependent manner. It is the protein expression of AQP-1 not the AQP-1 mRNA which were significantly different in different groups, suggesting that AZ affected AQP-1 in the post-transcriptional stage.
Objective To study the relationship between Th1/Th2 cytokines messenger ribonucleic acid (mRNA) expression and immune tolerance to cardiac allografts in rats. Methods Male DA rat hearts were transplanted to male Lewis rats using Ono’s model and randomly divided into three groups: control group, rejection group, and tolerance group (each group 10 rats). Mean survival time (MST), histological changes, mRNA expression level of Th1/Th2 cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4(IL-4), interleukin-10(IL-10) were measured. Results MST (85.28±7.48 d) of heart allografts in tolerance group was significantly longer than that(7.33±1.03 d) in rejection group. Only a few inflammatory cells infiltrated in cardiac allografts in tolerance group. The mRNA expression of IL-2, IFN-γ (Th1 cytokines) in rejection group were much ber than those in control group, and in tolerance group were much lower; mRNA expression of IL-4, IL-10 (Th2 cytokines) in rejection group were much ...更多lower than those in control group,and in tolerance group were much ber than those in control group. Conclusions The dynamic equilibrium of Th1/Th2 cytokines is very important in immune tolerance. The deviation of Th1 to Th2 is one of the mechanisms in immune tolerance.
Objective To evaluate the cost-effectiveness of three LTBI screening strategies: the tuberculin skin test (TST), the T-SPOT.TB and the combination of TST and T-SPOT (TST+T.SPOT), to provide economic evidence for T.SPOT application in China. Methods A decision analysis model evaluated three strategies among a cohort of 1000 tuberculosis (TB) close contacts, using incremental cost-effectiveness of prevention a active TB patient (1 year post contact). Meta analyses were conducted to calculate the key parameters of T.SPOT and TST. The official data or literature was searched and the unaccessible data was to specify other parameters, such as cost, LTBI prevalence, etc. The one-way sensitivity analysis was performed, varying key parameters over a wide range of reasonable values to evaluate the impact of data uncertainties and to determine the robustness of our overall conclusion. Results a) As for the total cost, the TST+T.SPOT strategy (?212 213.81 per 1 000 contacts) cost the least, while the single T.SPOT strategy cost the most; b) Subsequently, the TST+T.SPOT strategy required less contacts to be treated to prevent an active case of TB (8.31) than the single TST strategy (25.67); c) the TST+T.SPOT strategy shared the most cost-effectiveness (?3 063.50 per active TB case prevented) than the single TST or T.SPOT strategy; and d) The results of one-way sensitivity analyses showed that cost-effectiveness values were sensitive to changes in LTBI prevalence (gt;60%), Sen and Spn of TST test (gt;70%), with the single TST being superior to the single T.SPOT. Conclusion The Single T.SPOT strategy enjoys the most cases prevented from active TB, while the TST+S.SPOT strategy is the most cost-effective. The conclusion is sensitive to a few parameters, such as LTBI prevalence, but the TST+T.SPOT strategy is always the best.
ObjectiveTo investigate the changes of plasma platelet activating factor (PAF) interleukin-8(IL-8) and interferon-γ (IFN-γ) in patients after surgery with extracorporeal circulation (ECC) and their clinical significance. MethodsSeventy-five patients undergoing surgery with ECC in the First College of Clinical Medicine,China Three Gorges University from June 2012 to June 2013 were enrolled in this study. According to the presence of postoperative acute lung injury/acute respiratory distress syndrome (ALI/ARDS) all the 75 patients were divided into 2 groups. In ALI/ARDS group, there were 28 patients including 20 male and 8 female patients with their age of 53.6±8.2 years. In the control group,there were 47 patients without postoperative ALI/ARDS,including 32 male and 15 female patients with their age of 56.9±11.8 years. Dynamic variations of plasma PAF,IL-8 and IFN-γ of these patients were examined with enzyme-linked immunosorbent assay (ELISA) and compared between the 2 groups. ResultsIn ALI/ARDS group,plasma IL-8 and IFN-γ reached peak levels at 48 hours after surgery and gradually decreased after that;plasma PAF reached the peak level at 96 hours after surgery and gradually decreased after that. Postoperative plasma PAF (96 hours after surgery:16 029.5±4 203.7 mU/ml vs. 4 520.1±312.2 mU/ml,P<0.05) IL-8 (48 hours after surgery:48 580.5±8 095.8 pg/ml vs. 5 990.5±1 179.0 pg/ml,P<0.05) and IFN-γ (48 hours after surgery:258.5±76.1 pg/ml vs. 26.1±11.5 pg/ml,P<0.05) of ALI/ARDS group were significantly higher than those of the control group at 48 hours,96 hours and 144 hours after surgery. ConclusionPlasma PAF,IL-8 and IFN-γ change significantly after surgery with ECC,which may play an important role in the pathogenesis of postoperative ALI/ARDS.
ObjectiveTo evaluate the diagnostic value of interferon-gamma release assay (TB-IGRA) for tuberculosis in the Tibetan. MethodsFrom January 2014 to December 2014, suspected Tibetan tuberculosis patients were enrolled from AVIC 363 Hospital and underwent TB-IGRA test. All patients were also underwent smear test for Mycobacteria. The diagnostic value of TB-IGRA test for Tibetan TB patients was analyzed. ResultsA total of 77 suspected Tibetan tuberculosis patients were included. According to the diagnostic criteria, of the 77 suspected patients, 50 were diagnosed as TB patients, and 27 were diagnosed as not-TB patients. The sensitivity and specificity of TB-IGRA test was 86% and 81.5%. While the sensitivity and specificity of smear test were 22% and 100%, respectively. ConclusionThe TB-IGRA test is superior to smear test, and is the fast and sensitivity test for diagnosing Tibetan TB patients.
ObjectiveTo investigate the expression of programmed cell death-1 (PD-1), interferon-γ (IFN-γ), interleukin-4 (IL-4) and T help cells (Th) in peripheral blood of patients with asthma.MethodsForty-one asthma patients were divided into an acute group (20 cases) and a chronic group (21 cases) according to the disease state of asthma. Another 18 healthy subjects were recruited as a control group. Peripheral blood samples were collected from all the subjects at admission or inclusion. The concentrations of PD-1, IFN-γ and IL-4 were detected by enzyme-linked immunoassay method. The expressions of Th1 and Th2 were detected by flow cytometry method.ResultsThe PD-1 and IFN-γ concentrations, Th1 proportion and Th1/Th2 ratio in the two asthma groups were reduced compared with the healthy control group, and were significantly lower in the acute group compared with the chronic group (all P<0.05). The IL-4 level and Th2 proportion in the two asthma groups were increased compared with the healthy control group, and were significantly higher in the acute group than the chronic group (allP<0.05). In the acute group, the PD-1 level was positively correlated with IFN-γ and Th1 level (r values were 0.678 and 0.712, respectively), and negatively correlated with IL-4 and Th2 (r values were –0.745 and –0.700, respectively).ConclusionThe concentration of PD-1 in patients with asthma is reduced especially in acute asthma, and shows close correlation with conventional index of asthma.