Does choice of antiretroviral drugs matter for inflammation?

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut.

Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies.

Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.     

利培酮和齐拉西酮对精神分裂症患者血浆细胞因子的影响

目的:研究抗精神病药对精神分裂症患者细胞因子的影响。方法:符合ICD-10精神分裂症诊断的60名患者,随机分为利培酮组(给予利培酮治疗)和齐拉西酮组(给于齐拉西酮治疗),并以健康对照组比较,对患者在治疗前及治疗8周后测量血浆IL-2、IL-6及TNF-α水平,并对患者进行PANSS量表评定。结果:两组患者治疗前后血浆IL-2、IL-6及TNF-α水平与对照组比较,差异有统计学意义(P0.05)。两组患者治疗后血浆IL-2、IL-6及TNF-α水平较治疗前降低,差异有统计学意义(P0.05)。治疗前IL-2水平与PANSS量表阳性症状评分呈正相关(r=0.54,P0.05)治疗后TNF-α与阴性症状分呈显著正相关(r=0.41,P0.05)。结论:精神分裂症患者存在免疫功能异常,利培酮和齐拉西酮可以降低精神分裂症患者细胞因子水平。细胞因子水平与精神病理存在一定相关性。     

Influence of Statins on Circulating Inflammatory Cytokines in Patients With Abnormal Glucose Homeostasis: A Meta-analysis of Data From Randomized Controlled Trials

PurposeChronic inflammation increases the risks for cardiovascular disease, type 2 diabetes, and cancer. Recently, the antiinflammatory effects of statins, as cholesterol-lowering medications, have been considered. This study systematically reviewed and summarized earlier findings from randomized clinical trials about the effects of statins on serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6 in patients with abnormal glucose homeostasis.MethodsRelevant articles published through October 2019 were searched using suitable key words on the PubMed/MEDLINE, SCOPUS, EMBASE, and Google Scholar databases. RCTs were included if they compared the effects of statins on serum concentrations of CRP and IL-6 in adults with abnormal glucose homeostasis. The effect sizes were represented as weighted mean differences (WMDs) and 95% CI s using a random-effects model. Subgroup analysis was performed to find possible sources of heterogeneity.FindingsOverall, 17 publications with 21 effect sizes and which enrolled 3766 subjects (1895 participants in intervention and 1871 in control groups) were included. Combining 13 effect sizes from 10 studies, a significant reduction in serum CRP concentration following the administration of atorvastatin was found (WMD, −0.35; 95% CI, −0.54 to −0.17; I² = 90.6%). Based on 5 effect sizes from 4 studies, we found a statistically significant reduction in serum IL-6 concentration after atorvastatin therapy (WMD, −0.44; 95% CI, −0.65 to −0.22; I² = 93.9%). Pooling 6 effect sizes from 5 studies revealed a significantly reduced serum concentration of CRP after simvastatin therapy (WMD, −0.66; 95% CI, −0.79 to −0.54; I² = 97.6%).ImplicationsThe administration of atorvastatin or simvastatin in patients with abnormal glucose hemostasis was associated with a reduced serum CRP concentration. Atorvastatin therapy might also help to decrease serum IL-6 concentration in these patients.     

肥胖与骨质疏松症关系的研究进展

肥胖是许多慢性疾病的危险因素。肥胖与骨之间的病理生理关系是复杂的,最近来自流行病学和动物研究的数据表明:脂肪堆积对骨密度不利。肥胖可能通过多种机制影响骨代谢,由于脂肪细胞和成骨细胞起源于共同的多能间充质干细胞,肥胖能增强脂肪细胞分化并促进脂肪积累,进而减少成骨细胞分化和骨形成。肥胖与慢性炎症有关,在肥胖患者中,循环血液和组织的促炎细胞因子水平增加,从而通过修饰NF-κB(RANK)/RANKL/骨保护通路的受体活性,而增进破骨细胞活性并加速骨吸收。此外,肥胖患者中脂肪细胞分泌瘦素过多和(或)脂联素生成过少可能直接影响骨形成或通过上调促炎细胞因子而间接影响骨吸收。另外,高脂摄入可能干预肠道钙吸收而降低成骨可利用的钙量。本篇叙述了肥胖对骨代谢影响的作用机制,阐明脂肪和骨代谢之间在分子水平的关系,有助于开发预防或治疗肥胖和骨质疏松的治疗性药剂。     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

肠道病毒71型感染手足口病患儿Th1/Th2细胞因子变化

目的探讨肠道病毒71型(EV71型)感染手足口病患儿的常规生化检查及辅助性T细胞(help T cell,Th)1/Th2细胞因子变化。方法选择儋州市人民医院2017年1月-2018年12月住院的EV71型感染手足口病患儿120例作为研究对象,其中普通型67例,重症型53例。另选择医院2017年1月-2018年12月健康体检小儿60名作为对照组。对两组患儿白细胞计数(WBC)、C-反应蛋白(CRP)、白细胞介素-2(IL-2)、IL-4、IL-6、IL-10和干扰素-γ(IFN-γ)水平进行比较。结果感染组WBC计数、CRP、IL-2、IL-4、IL-6、IL-10和IFN-γ含量分别为(12.01±1.24)×10^9/L、(10.83±2.45)mg/L、(10.83±1.24)pg/ml、(11.43±1.46)pg/ml、(34.39±5.46)pg/ml、(10.32±2.41)pg/ml、(4.83±0.97)pg/ml,均高于对照组,差异均具有统计学意义(P<0.05)。重症组WBC计数、CRP、IL-2、IL-4、IL-6、IL-10和IFN-γ含量高于普通组,差异均具有统计学意义(P<0.05)。结论EV71型感染手足口病患儿WBC计数和CRP水平升高,且Th1/Th2细胞因子IL-2、IL-4、IL-6、IL-10和IFN-γ明显升高,且与病情进展密切相关。     

HMGB‐1, TLR4, IL‐1R1, TNF‐α, and IL‐1β: novel epilepsy markers?

Aim: The purpose of this study was to compare HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels in patients with mild and severe epilepsy with those in a healthy control group. Methods: Children aged 4–17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB‐1, TLR4, IL‐1R1, TNF‐α and IL‐1β levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. Results: HMGB‐1, TLR4, TNF‐α, and IL‐1β levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL‐1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). Conclusion: In this first report to identity a possible correlation between HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug‐refractory epilepsy.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.