Interleukin-1β:Friend or foe for gastrointestinal cancers

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections

BACKGROUND Mycoplasma pneumoniae(MP)frequently causes respiratory infections in children,whereas Epstein-Barr virus(EBV)typically presents subclinical manifestations in immunocompetent pediatric populations.The incidence of MP and EBV coinfections is often overlooked clinically,with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.AIM To evaluate the serum concentrations of interleukin-2(IL-2)and interleukin-12(IL-12)in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.METHODS We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection,isolated MP infection,and a control group of healthy children,spanning from January 1,2018 to December 31,2021.Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay.Logistic regression was employed to identify factors influencing poor prognosis,while receiver operating characteristic(ROC)curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.RESULTS The co-infection group exhibited elevated serum IL-2 and C-reactive protein(CRP)levels compared to both the MP-only and control groups,with a reverse trend observed for IL-12(P<0.05).In the poor prognosis cohort,elevated CRP and IL-2 levels,alongside prolonged fever duration,contrasted with reduced IL-12 levels(P<0.05).Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes(P<0.05).ROC analysis indicated that the area under the curves for IL-2,IL-12,and their combination in predicting poor prognosis were 0.815,0.895,and 0.915,respectively.CONCLUSION Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis,with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Interleukin-1:an important target for perinatal neuroprotection?

Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral palsy.Extensive clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain growth.Multiple pathways are involved in the pathogenesis of perinatal inflammation.However,studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine interleukin-1.In this review,we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain injury.We also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage,and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist,anakinra,as a safe and effective therapeutic intervention.We reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment,and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

The role of Interleukin-1 family in cardiovascular disease and its research progress

The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation.Moreover,accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases.Therefore,we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases,including atherosclerosis,myocardial infarction and heart failure.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

Drug-induced entero-colitis due to interleukin-17 inhibitor use;capsule endoscopic findings and pathological characteristics:A case report

BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.

6-Gingerol, asarinin, and deoxyschizandrin improve bronchial epithelium functions in an interleukin-13einduced BEAS-2B cell model

Objective:To explore the effects of 6-gingerol,asarinin,and deoxyschizandrindthe main components of Zingiber officinale(Willd.)Rosc.(Gan Jiang),Asarum heterotropoides f.var.mandshuricum(Maxim.)(Xi Xin),and Schisandra chinensis(Turcz.)Baill.(Wu Wei Zi),respectivelydon an interleukin(IL)-13einduced BEAS-2B cell model in vitro.Methods:The BEAS-2B cell model was established using 25 ng/mL IL-13 combined with 1%fetal bovine serum(FBS)in vitro.Mitoquinone mesylate(Mito-Q)treatment was used as a positive control group,and different concentrations of 6-gingerol,asarinin,and deoxyschizandrin were used to treat the models.The level of reactive oxygen species(ROS)production was detected by flow cytometry.The expression levels of LC3B,Beclin1,adenosine 50-monophosphate(AMP)eactivated protein kinase(AMPK),phosphory-lated-AMPeactivated protein kinase(P-AMPK),dynamin-related protein 1(DRP1),and mitochondrial fusion protein 2(MFN2)were detected by Western blot.Mitochondrial membrane potential(MMP)assay kit with JC-1 was utilized to detect the level of MMP.Results:The BEAS-2B cells exposed to 25 ng/mL IL-13 with 1%FBS showed an increased ROS level and a decreased MMP.6-Gingerol,asarinin,and deoxyschizandrin were able to downregulate ROS level and upregulate the MMP in the BEAS-2B model.Asarinin and deoxyschizandrin reduced the expression of autophagy protein LC3B,while deoxyschizandrin significantly increased the expression of DRP1 in the BEAS-2B model.Conclusion:6-Gingerol,asarinin,and deoxyschizandrin can reduce ROS generation and increase MMP,but have different regulatory effects on the expression of autophagy protein and mitochondrial mitotic protein.The three components have both synergistic and complementary effects in classic medicine compatibility.This study may provide an innovative strategy to reduce the lung inflammation related to IL-13.

The remedial effect of soluble interleukin-1 receptor type Ⅱ on endometriosis in the nude mouse model

Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.

Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis

AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.

血清中Interleukin-18含量的检测对结肠癌预后判断的价值

目的 探讨结肠癌患者血清中白细胞介素 18(IL 18)水平与预后的关系。方法 收集 10 6例结肠癌患者和 60例健康成人的血清 ,采用酶联免疫吸附反应 (ELISA )检测IL 18的水平。结果 1997年 6月及以前的血清 5 9份 ,IL 18的平均含量为3 3 8.46pg/ml ;1997年 6月以后的血清 47份 ,IL 18的平均含量为 3 2 8.85 pg/ml ;2组比较无显著性差异 (P <0 .0 5 ) ;结肠癌组患者血清IL 18的含量 ( 3 46.5 3 pg/ml± 3 1.2 3pg/ml)明显高于正常对照组 ( 2 3 3 .3 2 pg/ml± 2 2 .5 4pg/ml) ,有显著性差异 (P <0 .0 5 ) ;Ⅱ期、Ⅲ期和Ⅳ期患者血清中IL 18水平明显高于对照组 (P <0 .0 5 ) ,血清IL 18≥ 3 46pg/ml组的患者 5年生存率为 5 .3 % ,血清IL 18<3 46pg/ml的患者 5年生存率为 18.6% ;两组比较有显著性差异 (P <0 .0 5 ) ;多因素分析表明 ,血清IL 18含量是判断结肠癌患者预后的独立因素。结论 血清中IL 18含量与结肠癌患者 5年生存率有密切相关。血清中IL

Relationship of Serum Interleukin-18 and Interleukin-12 Levels with Clinicopathology in Renal Cell Carcinoma

Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.

Interleukin-1 receptor antagonist:From synthesis to therapeutic applications

The cytokine channel’s mechanism for self-regulation involves the application of antagonistic cytokines that are synthesized to connect to the receptors and release soluble cytokine receptors.The very first receptor antagonist of cytokine that was naturally present was interleukin-1 receptor antagonist(IL-1Ra).The IL-1Ra protein forms are disinfected from supernatants of cultured monocytes on stacked IgG.The family of IL-1 consists of IL-1α,IL-1βand IL-1Ra.Human monocytes regulate the production of IL-Ra.IL-Ra takes part in normal physiological functions by using specific antibodies,and acts as an anti-inflammatory agent.IL-Ra is synthesized in the tissues during the period of active disease and can be systematically measured and/or estimated.Maintenance of the levels of IL-Ra and IL-1 is the main factor for host resistance in patients during diseased conditions,as IL-Ra acts as an inherent regulator of various inflammatory responses.In this article,we focuse on how IL-Ra is synthesized and performs its functions once the inflammatory responses are activated.

ILTV Glycoprotein B(gB)与鸡Interleukin-18(IL-18)真核双表达载体的构建及表达

将ILTVgB基因和鸡IL-18基因插入到真核双表达载体pIRES中,构建共表达gB和IL-18基因的重组质粒pIRES-gB/IL18和表达gB基因的pIRES-gB质粒。通过脂质体将其转染鸡胚成纤维细胞,利用RT-PCR及间接免疫荧光检测重组质粒在体外的表达。将重组质粒通过腿部肌肉多点注射免疫21日龄雏鸡,应用ELISA和流式细胞仪分别检测免疫鸡的体液免疫及细胞免疫水平。结果显示,pIRES-gB/IL18和pIRES-gB转染细胞中分别含gB/IL-18基因的mRNA和gB基因的mRNA。间接免疫荧光检测表明,pIRES-gB/IL18和pIRES-gB在CEF细胞中有效地转录并表达gB蛋白。pIRES-gB/IL18和pIRES-gB免疫雏鸡后均能促进外周血T淋巴细胞亚群数量和血清中特异性抗体水平的增加,但前者的免疫效果明显优于后者,表明gB基因和鸡IL-18基因均获得了表达,且鸡IL-18能明显增强ILTV DNA疫苗诱发的免疫应答。

Acupuncture at the “Huatuojiaji” point affects nerve root regional interleukin-1 level in a rat model of lumbar nerve root compression

BACKGROUND：It has been shown that interleukin-1 （IL-1） may cause inflammatory reactions, which stimulate the nerve root of patients with lumbar intervertebral disc protrusion and leads to pain. Whether the clinical curative effects of acupuncture in the treatment of lumbar and leg pain are linked to an inhibition of local IL-1 secretion is unknown. OBJECTIVE： To assess the influence of acupuncture on IL-1, this study was designed to verify the effects of acupuncture at the ＂Huatuojiaji （Extra）＂ point on the nerve root in a rat model of lumbar nerve root compression, compared with administration of meloxicam, a non-steroidal anti-inflammatory drug. DESIGN, TIME AND SETTING： Randomized, controlled, molecular biology experiment, performed at the Experimental Center, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University between September 2005 and April 2006. MATERIALS： Forty healthy adult Sprague Dawley rats of either gender were included in this study. The rats were randomly and evenly divided into the following four groups： normal control, model, acupuncture and meloxicam groups. Lumbar nerve root compression was induced in rats in the model, acupuncture, and meloxicam groups by inserting a specially made silicon rubber slice at the juncture of the L5 nerve root and the dural sac. The acupuncture needle （pattern number N3030, 30#, 1.5 inch） was purchased from Suzhou Medical Appliance Factory, China. IL-1 enzyme linked immunosorbent assay （ELISA） kit was purchased from Santa Cruz Biotechnology, Inc., USA. METHODS： The acupuncture group was acupunctured at the ＂Huatuojiaji＂ point, which is lateral to the compressed L5-6 nerve root, with an acupuncture depth of 0.5 cm. There were two treatment courses, each of involved seven 20-minute acupuncture sessions, one session a day. The meloxicam group was administered intragastrically 3.75 mg/kg meloxicam （5 mg meloxicam /10 mL physiological saline）. Rats in the normal control group and model group received an intragastric administration of 10 mL/kg physiological saline. All administrations were performed once a day. MAIN OUTCOME MEASURES： At day 14 post-surgery, the IL-1 level in the compressed nerve root was determined by a streptavidin-peroxidase （S-P） immunohistochemical method, and IL-1β mRNA expression in the compressed nerve root was simultaneously detected by real-time reverse transcription-polymerase chain reaction. RESULTS： The expression levels of IL-1 and IL-1β mRNA in the L5 nerve root were significantly higher in the model group than in the control group （P 〈 0.01）. However, the expression levels of IL-1 and IL-1β mRNA were significantly lower in the acupuncture and meloxicam groups than in the model group （P 〈 0.05–0.01）. Expression levels of IL-1 and IL-1β mRNA were significantly higher in the acupuncture group than in the meloxicam group （P 〈 0.01）. CONCLUSION： Acupuncture at the ＂Huatuojiaji＂ point decreases the IL-1 level by inhibiting IL-1β mRNA expression to a greater extent than meloxicam administration.

Interleukin-1α, 6 regulate the secretion of vascular endothelial growth factor A, C in pancreatic cancer

Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells-stromal cell interaction , which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-lct (EL-1α), and interleukin-6 (IL-6). METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer,we used the reverse transcription -polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1α (10μg/L) or IL-6 (100 μg/L). RESULTS:Northern blot analysis revealed the presence of the 4.1-kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-la, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but, no effect was found in the COLO-357 cell line. CONCLUSION:These findings suggested that the expression of VEGF-A, C and their regulation by IL-1α, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.

Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation

AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction;Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45-MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.