ObjectiveTo investigate the expression of interleukin-18（IL-18）and signal transducers and activators of transcription 5（STAT5）in retina of 4-24-week-old diabetic rats, and explore the potential molecular mechanisms involved in diabetic retinopathy (DR).MethodsRetinal gene expression profile of healthy and 8-week-old diabetic rats was established with restriction fragment differential displaypolymerase chained reaction (RFDD-PCR), and the differences was analyzed by bioinformatics. IL-18 and STAT5 were filtrated as the candidate genes of DR. The expression of IL-18 and STAT5 in retina of diabetic rats with the age of 4, 8, and 24 weeks was observed by semi-quantitative reverse transcriptase-polymerase chain reaction（RT-PCR）.ResultsThe result of RFDD-PCR showed:expression of IL-18 was higher in healthy retina than that in diabetic one; expression of STAT5 was not found in healthy rats but in diabetic ones. The result of RT-PCR showed：compared with the normal, high expression of IL-18 was found in 4-week diabetic retina, reduced in 8-week one, and decreased to the lowest in 24-week one. The expression of STAT5 was not observed in healthy or 4week diabetic retina, but occurred in 8-week one, and increased in 24-week one. ConclusionThe expression of IL-18 and the activation of STAT5 may relate to the occurrance of DR. The expression of IL-18 doesn′t depend on the activation of STAT5. (Chin J Ocul Fundus Dis, 2005,21:258-260)
【Abstract】Objective To investigate the role of interleukin-10（IL-10） and interleukin-18 （IL-18） in the pathogenesis of acute lung injury in experimental severe acute pancreatitis.Methods Forty-eight SD rats were divided into control group and SAP group by the random data table. The model of experimental severe acute pancreatitis was established by injection of 3.5% sodium taurocholate into the bili-pancreatic duct. Lung wet weight index, ascities and level of serum amylase, IL-10 and IL-18 were quantitatively measured in different time. Intrapulmonary expressions of IL-10 mRNA and IL-18 mRNA were detected by semiquantitative RTPCR. The histopathology of pancreas and lung were observed under the light microscope.Results Lung wet weight index, ascities, level of serum amylase, IL-10 and IL-18, intrapulmonary expressions of IL-10 mRNA and IL-18 mRNA were significantly increased in SAP group (P＜0.01). The level of serum IL-18 and intrapulmonary expression of IL-18mRNA are positively correlated with lung wet weight index （r=0.68,P＜0.01; r=0.72,P＜0.01） and lung injury score （r=0.74,P＜0.01; r=0.79,P＜0.01) respectively, whereas the level of serum IL-10 and intrapulmonary expression of IL-10 mRNA are negatively correlated with lung wet weight index（r=-0.62,P＜0.01; r=-0.69,P＜0.01） and lung injury score（r=-0.66,P＜0.01; r=-0.60,P＜0.01）. Conclusion IL-18 may play a key role in the pathogenesis of acute lung injury in experimental severe acute pancreatitis, and IL-10 exerts the protection role in this process.
Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.
Objective To study the expression of interleukin (IL)-37 and related factors in lung tissue of rats with acute lung injury, and explore the role and significance of IL-37 in acute lung injury so as to understand the pathogenesis of acute lung injury. Methods Forty-five clean-grade Wistar rats were randomly divided into a healthy control group, a bleomycin group and a dexamethasone treatment group, with 15 rats in each group. The rats in the bleomycin group and the dexamethasone group were treated with bleomycin at a dose of 4 mg/kg by intratracheal administration. The healthy control group was given the same volume of saline as control. The dexamethasone treatment group was injected with dexamethasone 3 mg/kg intraperitoneally twice a day on the basis of acute lung injury. The healthy control group and the bleomycin group were injected intraperitoneally with normal saline as control. The rats in each group were sacrificed at 7, 14 and 28 days after modeling. The histopathological changes of lung tissue were evaluated by HE staining. The levels of IL-37 in lung homogenate and tumor necrosis factor (TNF)-α in serum were measured. The expression of IL-18 mRNA in lung tissue was detected by RT-PCR. Results Pathological morphology showed that the lung tissue of the healthy control group was complete, no inflammatory and fibrotic changes at all time points. The lung tissues of the bleomycin group and the dexamethasone group manifested with acute alveolitis firstly and thus developed fibrosis changes lately, and the changes in the dexamethasone group were more slightly than those in the bleomycin group. The contents of IL-37 and TNF-α and the expression of IL-18 mRNA in the bleomycin group and the dexamethasone group reached to the highest point on the 7th day, and then decreased, but were significantly higher than those of the healthy control group on the 28th day (all P<0.05). Conclusions IL-37 plays an important role in the pathogenesis of acute lung injury in rats. This effect may be related to the regulation of IL-18 and TNF-α transduction.
Although the recent studies have concerned the pathogenesis and therapeutic strategies of acute kidney injury (AKI), the mortality of AKI is still terribly high, and it is still one of the most important death factors in the intensive care unit. There is no doubt that early verdict of AKI, is good for a more aggressive treatment and can promise an improved prognosis for AKI patients. Serum creatinine level, serving as the gold standard for diagnosis of kidney injury, cannot meet current clinical work in its sensitivity and specificity of diagnosis of early AKI. Over the past decades, researchers worked to find and verify novel AKI biomarkers, including neutrophil gelatinase associated lipocalin, interleukin-18, kidney injury molecule-1 and cystatin-C, which were proved to be the potential reliable predictor of AKI development and prognosis, and were of great importance to the early diagnosis and clinical monitoring of AKI. This paper reviews the main studies on these novel prognostic predictors of AKI over the decades and evaluates their roles and limitations in early diagnosis and clinical prognosis prediction.