Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （...Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo tumorigenesis.Results After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient mice.Conclusion Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.展开更多
Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) ...Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL 4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL 4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P <0.05), while cAMP and cAMP/cGMP were significantly lower than those in controls ( P <0.01). Plasma level of IL 4 was inversely correlated with forced expiratory volume at the first second (FEV 1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V 50 ) (both r =-0.46, P <0.05) while it was directly correlated with the scores of the clinical manifestations ( r =0.57, P <0.05) in COPD patients. Two weeks after treatment with theophylline, IL 4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/cGMP increased significantly ( P <0.05). The change of IL 4 was inversely correlated with the changes of FEV 1 and V 50 ( r =-0.53 and -0.54, respectively, P <0.05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL 4 might play a role in the pathoge nesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline's therapeutic effects of attenuating air flow limitation may partially depend on its anti inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL 4.展开更多
Summary： The relationship of interleukin-4 （IL-4） C-33T and C-590T （C-589T） gene polymorphisms with allergic rhinitis was analyzed. Data about the case control studies of IL-4 gene promoter polymorphisms [C-33T a...Summary： The relationship of interleukin-4 （IL-4） C-33T and C-590T （C-589T） gene polymorphisms with allergic rhinitis was analyzed. Data about the case control studies of IL-4 gene promoter polymorphisms [C-33T and C-590T （C-589T）] and their association with allergic diseases and correlation between serum IL-4 levels and allergic rhinitis were retrieved. The Stata 12.0 statistical soitvcare was applied to analyze the correlation between IL-4 gene polymorphisms and allergic rhinitis. The meta-analysis result of TT/CC genotype of -590 （-589） polymorphism showed a significant association with allergic diseases [OR=1.93, 95% CI （1.61 2.31）, P=0.00]. Meta-analysis of the TT＋TC versus CC genotype of IL-4 C-33/T polymorphism revealed significant associations with allergic diseases [OR=3.23, 95% CI （1.13-9.25）, P=0.03]. Meanwhile, there was a significant correlation between serum IL-4 levels and allergic rhinitis [OR=2.52, 95% CI-（1.80-3.23）, P=0.00]. IL-4 gene -590 TT genotype may increase the risk of allergic rhinitis and the T allele mutation of -33 might be correlated with aller- gic rhinitis.展开更多
Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of silicosis. Methods A case-control study was carried out. 101 si...Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of silicosis. Methods A case-control study was carried out. 101 silicosis patients were selected as cases. As strictly matching, 121 of non silicosis workers were selected as the controls. The polymophisms of IL-4 （five locus） were detected by the method of polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques. Results The GA genotype in the IL-4＋429 locus and the CC genotype in the IL-4＋448 locus were found. The frequencies ofAA, GG and AG of IL-4＋45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were 62.0%, 12.6%, and 26.4%. The differences between cases and controls were not significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and 29.8%. The differences were not significant. The frequencies of TT, CC, and CT in -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant （P=0.034）. Conclusion The relationship between genetic polymorphism of IL-4-33 site and silicosis has been found and -33TT is a protective genotype for silicosis.展开更多
Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also calle...Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.展开更多
Interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic cytokines.Recently,increasing ...Interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic cytokines.Recently,increasing evidence has suggested that autophagy regulates innate immunity by affecting M1/M2 polarization of microglia/macrophages.However,the role of interleukin-4 in microglial autophagy is unknown.In view of this,BV2 microglia were treated with 0,10,20 or 50 ng/mL interleukin-4 for 24,48,or 72 hours.Subsequently,light chain 3-II and p62 protein expression levels were detected by western blot assay.BV2 microglia were incubated with interleukin-4(20 ng/mL,experimental group),3-methyladenine(500μM,autophagy inhibitor,negative control group),rapamycin(100 nM,autophagy inductor,positive control group),3-methyladenine+interleukin-4(rescue group),or without treatment for 24 hours,and then exposed to amyloid-β(1μM,model group)or vehicle control(control)for 24 hours.LC3-II and p62 protein expression levels were again detected by western blot assay.In addition,expression levels of multiple markers of M1 and M2 phenotype were assessed by real-time fluorescence quantitative polymerase chain reaction,while intracellular and supernatant amyloid-βprotein levels were measured by enzyme-linked immunosorbent assay.Our results showed that interleukin-4 induced microglial autophagic flux,most significantly at 20 ng/mL for 48 hours.Interleukin-4 pretreated microglia inhibited blockade of amyloid-β-induced autophagic flux,and promoted amyloid-βuptake and degradation partly through autophagic flux,but inhibited switching of amyloid-β-induced M1 phenotype independent on autophagic flux.These results indicate that interleukin-4 pretreated microglia increases uptake and degradation of amyloid-βin a process partly mediated by autophagy,which may play a protective role against Alzheimer’s disease.展开更多
Summary： The present study aimed to examine the effect of intedeukin （IL）-4 on neutrophil chemo- taxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instill...Summary： The present study aimed to examine the effect of intedeukin （IL）-4 on neutrophil chemo- taxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat （rr） IL-4 （rrlL-4） at different doses [2, 4 or 8μ g/animal, dis- solved in 200 μL normal saline （NS）] or rrlL-4 at 4 μg/animal （dissolved in 200 μL NS）. NS （200 μL） and LPS （6 mg/kg/animal, dissolved in 200 IxL NS） were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrlL-4 （4 μg/animal） or LPS （6 mg/kg/animal）. The normal rats treated with different doses of rrlL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrlL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid （BALF） and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopa- thology by haematoxylin-eosin （HE） staining. The levels of cytokine-induced neutrophil chemoattrac- tant （CINC）-I and intercellular adhesion molecule （ICAM）-I in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of C1NCs （CINC-1, CINC-2u, CINC-2a, CINC-3） and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, C1NC-2a, CINC-2, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression oflCAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.展开更多
目的 研究急性胰腺炎(AP)患者外周血Toll样受体4(TLR4)、白细胞介素(IL)-1β、中性粒细胞/淋巴细胞比值(NLR)与疾病进展、预后的关系。方法 250例AP患者按病情分为轻症组(121例)、中重症组(89例)、重症组(40例),依据治疗5 d后预后情况...目的 研究急性胰腺炎(AP)患者外周血Toll样受体4(TLR4)、白细胞介素(IL)-1β、中性粒细胞/淋巴细胞比值(NLR)与疾病进展、预后的关系。方法 250例AP患者按病情分为轻症组(121例)、中重症组(89例)、重症组(40例),依据治疗5 d后预后情况分为预后不良组(33例)、预后良好组(217例)。对比不同时间点、不同病情及不同预后AP患者外周血TLR4、IL-1β、NLR水平,采用Pearson相关分析外周血TLR4、IL-1β、NLR与Ranson评分、淀粉酶的相关性,绘制受试者工作特征(ROC)曲线分析各指标诊断重症AP的价值,多因素Logistic回归分析预后危险因素。结果 AP患者入院24 h TLR4、IL-1β、NLR水平较入院48 h、72 h高(P<0.05);随病情加重,AP患者入院24 h TLR4、IL-1β水平升高,重症组NLR水平高于中重症组和轻症组(P<0.05);AP患者入院24 h TLR4、IL-1β、NLR水平与入院48 h Ranson评分及入院24 h淀粉酶水平均呈正相关(P<0.05);入院24 h TLR4、IL-1β、NLR联合预测重症AP的ROC曲线下面积、敏感度、特异度分别为0.895、84.53%、81.69%;预后不良组入院24 h TLR4、IL-1β、NLR水平高于预后良好组(P<0.05),且多因素Logistic回归分析显示入院24 h TLR4、IL-1β、NLR升高为AP患者预后不良的独立危险因素(P<0.05)。结论 AP患者外周血TLR4、IL-1β、NLR水平与疾病进展、预后有密切关联,可作为重要监测指标。展开更多
In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, t...In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, two site ELISA and RT PCR were applied to determine the level of IL 4 protein and mRNA expression in spleens respectively, clone forming units of infected kidneys were determined with the plating dilution method, and mean survival time of the mice was recorded. The results showed that, when compared with the controls, protein level of IL 4 increased in both intact mice infected with lethal doses of yeast (day 3, P <0.05; day 7, P <0 001) and immunosuppressed mice infected with sublethal doses of yeast (day 3, P >0.05; day 7, P <0.05). Furthermore, the level of IL 4 was higher on day 7 than on day 3 after infection ( P <0 001 and P <0.05 respectively in two groups). The tendency of IL 4mRNA expression was similar with that of IL 4 protein. As for fungal loads in kidneys, CFUs were significantly higher on day 7 than on day 3 after infection . Mice in both groups succumbed to infection within several days. It was suggested that IL 4 might play a promoting role in the development of murine systemic Candidiasis.展开更多
文摘Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo tumorigenesis.Results After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient mice.Conclusion Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.
文摘Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL 4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL 4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P <0.05), while cAMP and cAMP/cGMP were significantly lower than those in controls ( P <0.01). Plasma level of IL 4 was inversely correlated with forced expiratory volume at the first second (FEV 1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V 50 ) (both r =-0.46, P <0.05) while it was directly correlated with the scores of the clinical manifestations ( r =0.57, P <0.05) in COPD patients. Two weeks after treatment with theophylline, IL 4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/cGMP increased significantly ( P <0.05). The change of IL 4 was inversely correlated with the changes of FEV 1 and V 50 ( r =-0.53 and -0.54, respectively, P <0.05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL 4 might play a role in the pathoge nesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline's therapeutic effects of attenuating air flow limitation may partially depend on its anti inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL 4.
文摘Summary： The relationship of interleukin-4 （IL-4） C-33T and C-590T （C-589T） gene polymorphisms with allergic rhinitis was analyzed. Data about the case control studies of IL-4 gene promoter polymorphisms [C-33T and C-590T （C-589T）] and their association with allergic diseases and correlation between serum IL-4 levels and allergic rhinitis were retrieved. The Stata 12.0 statistical soitvcare was applied to analyze the correlation between IL-4 gene polymorphisms and allergic rhinitis. The meta-analysis result of TT/CC genotype of -590 （-589） polymorphism showed a significant association with allergic diseases [OR=1.93, 95% CI （1.61 2.31）, P=0.00]. Meta-analysis of the TT＋TC versus CC genotype of IL-4 C-33/T polymorphism revealed significant associations with allergic diseases [OR=3.23, 95% CI （1.13-9.25）, P=0.03]. Meanwhile, there was a significant correlation between serum IL-4 levels and allergic rhinitis [OR=2.52, 95% CI-（1.80-3.23）, P=0.00]. IL-4 gene -590 TT genotype may increase the risk of allergic rhinitis and the T allele mutation of -33 might be correlated with aller- gic rhinitis.
基金supported by the Science and Technology Department of Hebei Province,09276195D
文摘Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of silicosis. Methods A case-control study was carried out. 101 silicosis patients were selected as cases. As strictly matching, 121 of non silicosis workers were selected as the controls. The polymophisms of IL-4 （five locus） were detected by the method of polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques. Results The GA genotype in the IL-4＋429 locus and the CC genotype in the IL-4＋448 locus were found. The frequencies ofAA, GG and AG of IL-4＋45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were 62.0%, 12.6%, and 26.4%. The differences between cases and controls were not significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and 29.8%. The differences were not significant. The frequencies of TT, CC, and CT in -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant （P=0.034）. Conclusion The relationship between genetic polymorphism of IL-4-33 site and silicosis has been found and -33TT is a protective genotype for silicosis.
基金supported by the National Natural Science Foundation of China,Nos.81901994(to BZ)and 81571147(to XXX)the Natural Science Foundation of Hubei Province,China,No.2019CFC847(to WWG)the Fundamental Research Funds for the Central Universities,China,No.2042018kf0149(to ML)
文摘Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.
基金supported by the Natural Science Foundation of Liaoning Province of China,No.20170541036(to HYL)
文摘Interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic cytokines.Recently,increasing evidence has suggested that autophagy regulates innate immunity by affecting M1/M2 polarization of microglia/macrophages.However,the role of interleukin-4 in microglial autophagy is unknown.In view of this,BV2 microglia were treated with 0,10,20 or 50 ng/mL interleukin-4 for 24,48,or 72 hours.Subsequently,light chain 3-II and p62 protein expression levels were detected by western blot assay.BV2 microglia were incubated with interleukin-4(20 ng/mL,experimental group),3-methyladenine(500μM,autophagy inhibitor,negative control group),rapamycin(100 nM,autophagy inductor,positive control group),3-methyladenine+interleukin-4(rescue group),or without treatment for 24 hours,and then exposed to amyloid-β(1μM,model group)or vehicle control(control)for 24 hours.LC3-II and p62 protein expression levels were again detected by western blot assay.In addition,expression levels of multiple markers of M1 and M2 phenotype were assessed by real-time fluorescence quantitative polymerase chain reaction,while intracellular and supernatant amyloid-βprotein levels were measured by enzyme-linked immunosorbent assay.Our results showed that interleukin-4 induced microglial autophagic flux,most significantly at 20 ng/mL for 48 hours.Interleukin-4 pretreated microglia inhibited blockade of amyloid-β-induced autophagic flux,and promoted amyloid-βuptake and degradation partly through autophagic flux,but inhibited switching of amyloid-β-induced M1 phenotype independent on autophagic flux.These results indicate that interleukin-4 pretreated microglia increases uptake and degradation of amyloid-βin a process partly mediated by autophagy,which may play a protective role against Alzheimer’s disease.
基金supported by a grant from the National Natural Science Foundation of China(No.30770945)
文摘Summary： The present study aimed to examine the effect of intedeukin （IL）-4 on neutrophil chemo- taxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat （rr） IL-4 （rrlL-4） at different doses [2, 4 or 8μ g/animal, dis- solved in 200 μL normal saline （NS）] or rrlL-4 at 4 μg/animal （dissolved in 200 μL NS）. NS （200 μL） and LPS （6 mg/kg/animal, dissolved in 200 IxL NS） were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrlL-4 （4 μg/animal） or LPS （6 mg/kg/animal）. The normal rats treated with different doses of rrlL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrlL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid （BALF） and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopa- thology by haematoxylin-eosin （HE） staining. The levels of cytokine-induced neutrophil chemoattrac- tant （CINC）-I and intercellular adhesion molecule （ICAM）-I in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of C1NCs （CINC-1, CINC-2u, CINC-2a, CINC-3） and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, C1NC-2a, CINC-2, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression oflCAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.
文摘目的 研究急性胰腺炎(AP)患者外周血Toll样受体4(TLR4)、白细胞介素(IL)-1β、中性粒细胞/淋巴细胞比值(NLR)与疾病进展、预后的关系。方法 250例AP患者按病情分为轻症组(121例)、中重症组(89例)、重症组(40例),依据治疗5 d后预后情况分为预后不良组(33例)、预后良好组(217例)。对比不同时间点、不同病情及不同预后AP患者外周血TLR4、IL-1β、NLR水平,采用Pearson相关分析外周血TLR4、IL-1β、NLR与Ranson评分、淀粉酶的相关性,绘制受试者工作特征(ROC)曲线分析各指标诊断重症AP的价值,多因素Logistic回归分析预后危险因素。结果 AP患者入院24 h TLR4、IL-1β、NLR水平较入院48 h、72 h高(P<0.05);随病情加重,AP患者入院24 h TLR4、IL-1β水平升高,重症组NLR水平高于中重症组和轻症组(P<0.05);AP患者入院24 h TLR4、IL-1β、NLR水平与入院48 h Ranson评分及入院24 h淀粉酶水平均呈正相关(P<0.05);入院24 h TLR4、IL-1β、NLR联合预测重症AP的ROC曲线下面积、敏感度、特异度分别为0.895、84.53%、81.69%;预后不良组入院24 h TLR4、IL-1β、NLR水平高于预后良好组(P<0.05),且多因素Logistic回归分析显示入院24 h TLR4、IL-1β、NLR升高为AP患者预后不良的独立危险因素(P<0.05)。结论 AP患者外周血TLR4、IL-1β、NLR水平与疾病进展、预后有密切关联,可作为重要监测指标。
文摘In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, two site ELISA and RT PCR were applied to determine the level of IL 4 protein and mRNA expression in spleens respectively, clone forming units of infected kidneys were determined with the plating dilution method, and mean survival time of the mice was recorded. The results showed that, when compared with the controls, protein level of IL 4 increased in both intact mice infected with lethal doses of yeast (day 3, P <0.05; day 7, P <0 001) and immunosuppressed mice infected with sublethal doses of yeast (day 3, P >0.05; day 7, P <0.05). Furthermore, the level of IL 4 was higher on day 7 than on day 3 after infection ( P <0 001 and P <0.05 respectively in two groups). The tendency of IL 4mRNA expression was similar with that of IL 4 protein. As for fungal loads in kidneys, CFUs were significantly higher on day 7 than on day 3 after infection . Mice in both groups succumbed to infection within several days. It was suggested that IL 4 might play a promoting role in the development of murine systemic Candidiasis.
