Association Between IL-6 （Interleukin-6） and Iron Status in Rheumatoid Arthritis Patients

The study was performed to determine whether the srum concentrations of IL （interleukin）-6 are elevated in patients with RA （rheumatoid arthritis） and to investigate the relationship between IL-6 levels and iron status in RA patients. 95 serum samples were obtained, 70 of them from patients with RA who had visited the department of Rheumatology at Al-Sadder medical city in Najaf governorate （Iraq） and 25 age and sex-matched healthy controls. The authors assessed the clinical parameters of the disease, including ESR （erythrocyte sedimentation rate）, CRP （C-reactive protein）, and RF （rheumatoid factor）. Serum levels of iron and TIBC （total iron binding capacity） were measured spectrophotometrically, while TS% （transferrin saturation percentage） and transferrin concentration were calculated mathematically. Serum concentrations of IL-6 （interleukin-6） and ferritin were measured using an ELISA （enzyme-linked immunosorbent assay）. The results of serum concentration of IL-6 （interleukin-6） and ferritin were significantly elevated （P 〈 0.0001） in patients with RA compared to those of healthy controls. On the other hand, serum concentrations of iron, TIBC （total iron binding capacity）, TS% （transferrin saturation percentage） and transferrin concentration were significantly decreased in patients with RA compared with those of healthy controls. These findings suggest that anemia is the most frequent observations in patients with RA and mostly associative with increasing level of interleukin-6.

Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

Unmet Needs in the Treatment of Rheumatoid Arthritis

Biologics have greatly improved the management of rheumatoid arthritis (RA), demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Unmet therapeutic needs in RA remain;however, further advances require an understanding of issues left unaddressed under the current treatment paradigm. Most biologic-na?ve and biologic-pretreated patients who initiate a biologic therapy, for example, do not reach American College of Rheumatology 50% (ACR50) response, and few achieve remission. Responses are often not durable, prompting frequent treatment switching. Predictive markers are unavailable to guide therapy selection, and clinical trial data are lacking on whether a tumor necrosis factor inhibitor (TNFi) is the best first-line biologic and on the optimal sequence of use for the different biologics. Risk of serious infection is the major safety concern. Translating preclinical and clinical findings into new therapeutics may help address unmet needs. An increasing body of evidence indicates that the cytokine interleukin (IL)-17A represents an important therapeutic target;ongoing trials with IL-17A inhibitors will determine whether these agents can address some of the unmet needs associated with current biologics.

Study on effect of imbalance of TRAF-6, IRAK-1 and NALP3 inflammatory factors in patients with gouty arthritis

Objective:To explore the effect of imbalance of tumor necrosis factor receptor related factor-6(TRAF-6),interleukin 1 receptor associated kinase-1(IRAK-1)and neutrophil alkaline phosphatase-3(NALP3)in patients with gouty arthritis.Methods:The retrospective experiment was conducted on 105 patients with gouty arthritis admitted to our hospital(47 patients with acute onset and 58 patients with remission,namely group A and group B);meanwhile,another 61 healthy volunteers were selected for control,namely group C.The enrolling of the three groups was dated from May 2017 to May 2018,and TRAF-6,IRAK-1 and NALP3 of all subjects were tested through real-time fluorescence quantification(RT-PCR),and the correlation between the three inflammatory factors and gouty arthritis was compared.Results:1)Through treatment,ESR,BUA and total addiment in group A and B were higher than those in group C,among which the three indicators in group A were higher than those in group B(P<0.05),while CRP was lower than that of group C,and the two indicators in group A were lower than those in group B(P<0.05).2)There was no significant difference in the relative expression of TRAF-6 mRNA between group A and group B before treatment(P>0.05),significantly lower than group C(P<0.05);the above indicators of group A and group B were improved to some extent after treatment,but group A was still lower than group B(P<0.05),and the degree of improvement of group A was also lower than that of group C(P<0.05),while the degree of improvement of group B was not significantly different from that of group C(P>0.05).3)The relative expression level of IRAK-1mRNA in group A and group B before treatment showed no significant difference(P>0.05),but was also lower than that in group C(P<0.05).The relative expression level of IRAK-1mRNA in group A and group B increased to some extent after treatment,with group A significantly lower than group C(P<0.05),and group B showed no significant difference compared with group C(P>0.05).4)The relative expression level of NALP-3 mRNA in group A and group B showed no significant difference(P>0.05)before treatment,significantly higher than that in group C(P<0.05);the relative expression of NALP-3 mRNA in group A was not significantly decreased(P>0.05)after treatment,while that in group B was significantly decreased after treatment(P<0.05),indicating significant different compared with group A and group C.5)There was no correlation between)TRAF-6,ESR,CRP and total addiment(P>0.05);IRAK-1 was negatively correlated with CRP,BUA and total addiment(P<0.05);NALP-3 was negatively correlated with ESR and CRP(P<0.05).Conclusion:TRAF-6,IRAK-1 and NALP-3 are all under abnormal expression in the developing of new gouty arthritis,acting as important participants in promoting the occurrence,development and outcome of illness states,so the intervening measures should be taken.

Analysis of the Role of D-Dimer,Interleukin-6,and Interleukin-18 in Differential Diagnosis of Pediatric Refractory Mycoplasma pneumoniae Pneumonia

Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.

Immunopathogenesis of reactive arthritis:Role of the cytokines

Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitourinary infection, but once arthritis develops, the microorgan-ism is not found in the joint. The classical microbes as-sociated with ReA development include Gram-negative aerobic or microaerophilic bacteria containing LPS in their outer membrane. The immunopathogenic mechanisms involved in ReA development are still unknown. A hypothesis suggested that the bacteria probably persist outside the joint, at sites such as gut mucosa or lymph nodes, and bacterial antigens might then be transported to the joints. On the other hand, an altered immune response and the unbalanced production of cy-tokines have been reported in subjects with ReA. Currently, there is increased evidence to suggest that both mechanisms would operate in the immunopathogenesis of ReA. In this review we highlight recent advances on the role of cytokines in the ReA. Particularly, we discuss the roles of some pro- and anti-infammatory cytokines involved in the immunopathogenesis of ReA.

Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and synovial fluid of rheumatoid arthritis patients

Background Programmed cell death 5 （PDCD5） is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells. Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro, implying a potential role in rheumatoid arthritis （RA） pathogenesis. This study examined the expression of PDCD5 in serum and synovial fluid of RA patients, its effect on the expression of inflammatory cytokine, interleukin-17 （IL-17）, and the assessment of disease activity in RA. Methods PDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis （OA） were detected using enzyme-linked immunosorbent assay （ELISA）. Concentrations of serum PDCD5 in 40 healthy people were also detected as controls. As disease activity indices, C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, rheumatoid factor （RF）, and X-ray grading scale were also evaluated. Results Serum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls. Serum PDCD5 level was inversely correlated to CRP and ESR, and was significantly higher in the RF negative group than in the positive group. PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients. However, differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable. Conclusions PDCD5 affects RA pathogenesis. Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein. As PDCD5 levels correlated negatively with disease activity indices and IL-17 level, PDCD5 could become a target in the diagnosis and treatment of RA.

Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis

Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis （RA）, and to determine the relationship between the IL-23 level and disease activity in RA patients. Methods Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score （DAS28）, C-reactive protein （CRP）, rheumatoid factor （RF） levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay （ELISA）. The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Results The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. Conclusions The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.

Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis

Objective To determine whether interleukin-1α and 1β gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1β and rheumatoid arthritis (RA) motif gene. Methods IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1α-889 and IL-1β+3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1β 2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data.Results There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and the controls. The β2/2 genotype of IL-1β was more common in female RA patients compared with controls (P=0.001). A lower carriage rate of IL-1β 2 occurred in male RA patients (P=0.001). A higher carriage rate of IL-1α2 is associated with a higher ESR (P=0.008), HAQ score (P=0.03), and vit-D 3 (P【0.001), but conversely a lower SJC (p=0.002), a lower RF (P=0.002) and a lower BMD at the lumbar spine (P=0.001). A higher frequency of IL-1α1 is associated with a lower CRP value (P=0.009). An increased IL-1β2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P【0.001), ESR (P【0.001) and pain score (P=0.001) and a higher BMD at the lumbar spine (P=0.007), lower vit-D 3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time did not contribute to disease activity.Conclution Polymorphisms of the IL-β gene may affect the RA occurrence. Carriage of IL-1β2 polymorphisms is associated with more active disease in RA and the presence of both the IL-1α2 and the IL-1β1 allele in RA influences bone resorption.

Effect of Moxibustion on IL-1β and IL-2 in Rat Models of Rheumatoid Arthritis

Objective： To observe the influence on IL-1β and IL-2 in rat models with rheumatoid arthritis after moxibustion on Shenshu （BL 23） and Zusanli （ST 36） points, and to discuss the mechanism of moxibustion. Methods： Fifty male Wistar rats were divided randomly into 5 groups, control group, model group, drug group, moxibustion group, and laser group, 10 for each. Four groups except the normal group were built on the model of rheumatoid arthritis. The changes of body weight and plantar circumference were measured and the level of IL-1β, IL-2 in sera were examined by ELISA. Results： Compared with the model group, the weight and plantar circumference of rats in the moxibustion group were improved significantly after treatment （P〈0.01）, and the improvement of plantar circumference also had significant differences compared with the drug group and the laser group （P〈0.05）. The level of IL-1β, IL-2 in sera were down regulated in the moxibustion group and the laser group, which had statistical differences compared with the model group （P〈0.05）, but no statistical differences were found when comparing with the drug group. Conclusion： Moxibustion obviously improves the toe tumefaction of the rats with rheumatoid arthritis, which is better than CO2 laser of 10.6μm. On the aspect of decreasing the amount of IL-1β, IL-2, CO2 laser of 10.6μm is similar with moxibustion.

Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease Activity and Ameliorated Inflammation in Synovial Fibroblasts

Background：Much evidence has demonstrated that interleukin （IL）-33 plays an important role in rheumatoid arthritis （RA）.However,there have been limited studies about soluble ST2,a receptor for 1L-33,in RA.The aims of this study were to detect the levels of ST2 in the serum and synovial fluid of RA patients and to reveal the association of these levels with disease activity and the function of ST2 in RA.Methods：A total of 56 RA patients and 38 age-matched healthy controls were enrolled in this study.Synovial fluid samples were collected from another 30 RA patients and 20 osteoartbritis patients.Serum and synovial fluid levels of ST2 were measured by ELISA.In addition,the levels of ST2 in the serum of RA patients before and after therapy were detected.The function of ST2 in RA was revealed by the results of an in vitro cell assay,where recombinant ST2 proteins were used to treat peripheral blood mononuclear cells （PBMCs） and RA synovial fibroblasts （RASFs）.Results：Serum-soluble ST2 levels were significantly higher in RA patients （127.14 ± 61.43 pg/ml） than those in healthy controls （78.37 ± 41.93 pg/ml,P 〈 0.01）.Synovial fluid-soluble ST2 levels （41.90 ± 33.58 pg/ml） were much higher in RA patients than those in osteoarthritis patients （19.71 ± 16.72 pg/ml,P 〈 0.05）.RA patients who received effective therapy for 6 months showed decreased serum-soluble ST2 levels （113.01 ± 53.90 pg/ml） compared to baseline （139.59 ± 68.36 pg/ml） （P =0.01）.RA patients with high disease activity had higher serum-soluble ST2 levels （162.02 ± 56.78 pg/ml） than those with low disease activity （94.67 ± 40.27 pg/ml,P =0.001）.Soluble ST2 did not affect IL-1β,IL-6,IL-8,or tumor necrosis factor-α （TNF-o） expression in PBMCs from RA patients.However,soluble ST2 ameliorated the expressions of IL-33 and IL-1 β but not that of IL-6,IL-8,or TNF-α in resting RASFs.Interestingly,in the RASFs stimulated by TNF-α plus IL-1 β,soluble ST2 showed extensive suppressive effects on the expression of IL-6,IL-8,and TNF-α.Conclusion：Elevated levels of ST2 in the serum and synovial fluid were associated with disease activity and ameliorated IL-33 expression and IL-33-induced inflammation in RASFs,suggesting that soluble ST2 might be a potential therapeutic candidate for RA.

Effect of adjuvant therapy with electroacupuncture on bone turnover markers and interleukin 17 in patients with rheumatoid arthritis

OBJECTIVE: To evaluate the effect of electroacupuncture as an adjuvant treatment with first-line medications on bone metabolism biomarkers and interleukin-17(IL-17) in the peripheral blood of patients with rheumatoid arthritis(RA).METHODS: Sixty RA patients were randomized into three groups. The control group was treated with methotrexate plus leflunomide(MTX + LEF),the acupuncture group was treated with simple needling plus MTX + LEF, and the patients in the electroacupuncture(EA) group were treated with EA plus MTX + LEF. EA or acupuncture was applied every other day for a total of 10 times over a treatment period of 8 weeks.RESULTS: In all three treatment groups, serum levels of the bone metabolism markers PICP, N-MID,and B-ALP were elevated and the concentrations of the inflammatory markers β-CTx, IL-17, CRP, and TRACP-5b were reduced after treatment. These differences were significant for the EA group but not the other groups(P < 0.05).CONCLUSION: EA could effectively reduce the suffering and improve the quality of life of RA patients. It is a promising adjuvant therapy for enhancing the effectiveness of clinical therapeutics.

IL-6和IL-18基因启动子多态性与广东汉族人群类风湿性关节炎相关性研究

目的了解我国广东地区汉族人群白细胞介素-6(IL-6)和白细胞介素-18(IL-18)基因启动子单核苷酸多态性及与类风湿性关节炎(RA)的相关性。方法应用序列特异性引物-聚合酶链反应(PCR-SSP)技术检测168名健康体检者和120例RA患者的IL-6基因启动子-572和-174及IL-18基因启动子-607C/A和-137G/C单核苷酸多态性。结果对照组和患者组IL-6基因启动子-572位点、-174位点和IL-18基因启动子-607C/A位点、-137G/C位点均存在单核苷酸多态性。IL-6-572位点、-174位点和IL-18-607位点基因型和等位基因频率分布在RA组和对照组间差异均有显著性(P<0.001)。IL-18-137位点基因型频率在两组间无统计学意义(P=0.141),但等位基因分布频率在两组间差异有显著性(P=0.024)。经Logistic回归分析,年龄、性别、IL-6-572位点、-174位点和IL-18-137位点与RA有相关性(P<0.05)。结论广东汉族人群IL-6基因启动子-572和-174单核苷酸多态性与RA可能相关,IL-18基因启动子-607C/A和-137G/C单核苷酸多态性与RA是否相关需进一步研究。

类风湿性关节炎辨证分型与白细胞介素6、18血清水平的关系

目的:探讨白细胞介素6(IL-6)和白细胞介素18(IL-18)血清水平与类风湿性关节炎(RA)中医辨证分型的关系。方法:采用酶联免疫吸附试验(ELISA)双抗体夹心法检测RA患者和健康人的外周血IL-6和IL-18的血清水平,分析不同证型两指标之间及其与C反应蛋白、类风湿因子含量的相关性。结果:RA患者IL-6和IL-18血清水平与健康人比较差异具有显著性,活动期RA患者IL-6水平显著高于稳定期患者(P<0.05)。风寒湿阻型患者血清IL-6浓度明显高于痰瘀互结型与肝肾两虚型(P<0.05),而与风湿热郁型无明显差异(P>0.05);而风寒湿阻型患者血清IL-18浓度明显高于风湿热郁型与肝肾两虚型(P<0.05),而与痰瘀互结型无明显差异(P>0.05)。结论:IL-6血清水平与RA的活动性密切相关,且与其中医辨证分型存在一定的联系。

类风湿性关节炎患者IL-6、IL-18和CRP的水平变化及意义

目的:研究类风湿性关节炎(RA)患者血清白细胞介素-6(IL-6)、白细胞介素-18(IL-18)和C-反应蛋白(CRP)水平的变化及其临床意义。方法:收集84例RA患者,以70例健康体检者作对照。采用双抗体夹心酶联免疫吸附法测定血清IL-6、IL-18和免疫荧光法测定CRP的水平,并测定血小板计数(Plt)、血沉(ESR)、类风湿因子(RF)。结果:RA患者的血清Plt、ESR、RF、IL-6、IL-18和CRP的含量明显高于健康对照组(P<0.01)。RA患者活动期上述指标含量(除RF外)均显著高于稳定期(P<0.01),Plt升高RA患者组与Plt正常组相比,RF、ESR、IL-6、IL-18和CRP水平均有明显统计学差异(P<0.05)。结论:IL-6、IL-18和CRP在RA患者的疾病发展过程中发挥着重要作用,它们的水平变化与RA患者病情有关,联合动态监测有助于临床观察RA患者的病情变化和治疗效果。

人疱疹病毒6型感染及IL-18基因多态性与类风湿性关节炎易感性的关联

目的探讨人疱疹病毒6型(HHV 6)感染及白细胞介素-18(IL-18)基因多态性与类风湿性关节炎(RA)易感性的关联。方法选取2019年12月-2021年12月丽水市人民医院收治的80例RA患者为研究对象,为RA组,另选取同期80名健康体检者为对照组,采用巢式聚合酶链式反应(Nested-PCR)法检测外周血单个核细胞(PBMCs)、血浆中HHV 6 DNA,采用PCR定量扩增技术检测IL-18基因启动子区-607C/A位点、-137G/C位点基因多态性,采用多因素Logistic回归分析探究HHV 6感染、IL-18基因多态性与RA易感性的关联。结果两组PBMCs中HHV6 DNA阳性检出率比较,无统计学差异,但RA组血浆HHV6 DNA阳性检出率高于对照组(P<0.05);血清类风湿因子(RF)浓度≥60 IU/ml患者血浆HHV6 DNA阳性率较<60 IU/ml高(P<0.05),疾病高活动度患者血浆HHV6 DNA阳性率较病情缓解、中低活动度高(P<0.05);两组IL-18-607C/A基因型分布及等位基因频率比较,无统计学差异,但RA组IL-18-137G/C的GC基因型、C等位基因频率均高于对照组(P<0.05);多因素Logistic回归分析显示,血浆HHV6 DNA阳性者较阴性者RA发病风险升高倍3.089倍(95%CI:1.289~7.405),携带IL-18基因-137G/C位点(GC+CC)基因型者较GG型者RA发病风险增加2.524倍(95%CI:1.338~4.764)。结论HHV6活动性感染、IL-18-137G/C基因多态性可能与RA易感性有关。

Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The &#x0201c;two-hit&#x0201c; hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-&#x003b1;, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis

AIM： To investigate the relationship between ulcerative colitis （UC） clinical activity index （CAI） and circulating levels of IL-1ra, IL-10, IL-6 and IL-18. METHODS： Blood levels of IL-1ra, IL-10, IL-6 and IL-18 were measured in 31 patients with active UC, the mean CAI was 11.1, ranging from 5-25; and 12 healthy individuals as controls. Patients were given granulocyte and monocyte adsorptive apheresis （GMA） with Adacolumn. Leucocytes which bear the FcyR and complement receptors were adsorbed to the column leucocytapheresis carriers. Each patient could receive up to 11 GMA sessions over 8 wk. RESULTS： We found strong correlations between CAI and IL-10 （r = 0.827, P 〈 0.001）, IL-6 （r = 0.785, P 〈 0.001） and IL-18 （r = 0.791, P 〈 0.001）. IL-1ra was not correlated with CAI. Following GMA therapy, 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls. Further, blood levels of IL-1ra and IL-10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that adhered to the carriers. CONCLUSION： Elevated blood levels of IL-6 and IL-18 together with peripheral blood granulocytes and monocytes/macrophages in patients with active UC show activative behaviour and increased survival time can be proinflammatory and the targets of GMA therapy.

Early application of nerve growth factor affects serum inflammatory cytokine levels in neonatal hypoxic ischemic encephalopathy

BACKGROUND： It has been demonstrated that there are changes of various cytokines, chemokines and adhesion factors in neonatal hypoxic ischemic encephalopathy （HIE）. What are the changes of interleukin-6 and interleukin-18 in serum of HIE neonates.OBJECTIVE： To observe the dynamic changes of interleukin-6 and interleukin-18 in peripheral serum at different time after HIE in neonates, and analyze the possible therapeutic efficacy of early application of NGF.DESIGN： A non-randomized controlled observation synchronically.SETTING： Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University.PARTICIPANTS： Sixty neonates with HIE were selected from the Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University from January 2004 to October 2006, including 32 boys and 28 girls, who were all accorded with the diagnostic standards for moderate to severe HIE. The neonates were divided into two groups NGF-treated group （n =30）, HIE group （n =30）. The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF within 24 hours after birth. Those in the HIE group were given routine treatments. Meanwhile, 30 apneic normal neonates （17 boys and 13 girls） at the same period were selected as the control group. The gestational age was 37 - 42 weeks in all the three groups, the body mass at birth was 2 500 - 4 000 g. Informed contents were obtained from the relatives of all the enrolled neonates.METHODS： The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF （2 000 U） within 24 hours after birth, once a day, 10 days as a course. Those in the HIE group were given routine treatments. Blood samples （3 mL） were drawn from femoral vein in all the neonates 1, 3 and 7 days after birth. The levels of interleukin-6 and interleukin-18 in serum were detected with enzyme-linked immunoabsorbent assay （ELISA）.MAIN OUTCOME MEASURES： Serum levels of interlenkin-6 and interleukin-18 at 1, 3 and 7 days after birth.RESULTS： All the 60 HIE neonates and 30 normal neonates were involved in the final analysis of results.① Serum level of interleukin-6： The serum levels of interlenkin-6 at 1, 3 and 7 days after birth in the HIE group were all lower than those in the control group （P 〈 0.05）, and gradually recovered to the normal level as time prolonged. The serum levels of interleukin-6 at 1, 3 and 7 days after birth in the NGF-treated group were higher than those in the HIE group （P 〈 0.05）. ②Serum level of interleukin-18： The serum levels of interleukin-18 at 1, 3 and 7 days after birth in the HIE group were all higher than those in the control group （P 〈 0.05）, especially that at 3 days. The serum levels of interleukin-18 at 1, 3 and 7 days after birth in the NGF-treated group were lower than those in the HIE group （P 〈 0.05）.CONCLUSION： After hypoxic ischemia, the level of interleukin-6 was decreased and that of interleukin-18 was increased in peripheral serum in HIE neonates, while NGF could balance the levels of interleukin-6 and interleukin-18, adjust the immunological function, and protect the nerve cells.

加味四妙勇安丸治疗类风湿性关节炎的疗效研究

目的研究加味四妙勇安丸治疗类风湿性关节炎的疗效。方法60例患者按随机数字分组法分为对照组和治疗组，各30例，治疗组口服加味四妙勇安丸1丸／次，3次／d；对照组服用雷公藤多甙片1me／（kg·d），分2—3次口服，治疗6个月，治疗后评定疗效；分别在治疗前、后测定2组患者的白细胞介素-6（IL-6）和IL-18的浓度。结果治疗组治愈5例（16．7％），有效28例（93．3％）；对照组治愈2例（6．7％），有效22例（73．3％），2组治疗后与治疗前比较，2组间差异均有统计学意义（P〈0．01或P〈0．05）。对照组治疗后IL-6与IL-18分别为[（4．91±2．09）ng／LVS（6.74±4．33）ng／L，（243．1士51．6）ng／L vs（302．5±97．8）ng／L，P〈0．01]；治疗组治疗后IL-6与IL-18均较治疗前降低[（2．69±1．34）ng／Lvs（6．72±4．39）ng／L，（119．6±36．4）ng／Lvs（307．6±101．3）ng／L，P〈0．01]。结论加味四妙勇安丸可改善类风湿性关节炎患者的症状，可能是通过改变IL-6与IL-18的表达而实现，其具体的机制有待进一步研究。