老年慢性阻塞性肺疾病急性加重期患者IL-8、IL-6、TNF-α水平变化与肺功能的相关性研究

目的探讨老年慢性阻塞性肺疾病急性加重期(AECOPD)患者IL-8、IL-6、TNF-α水平变化和肺功能的相关性。方法选取我院收治的AECOPD患者78例。分别于患者急性加重期和稳定期检测其血清IL-8、IL-6、TNF-α水平以及肺功能。对比不同肺功能综合评估分级的患者IL-8、IL-6、TNF-α的水平,同时对比急性加重期和稳定期患者IL-8、IL-6、TNF-α和FEV1%预计值的检测结果,并分析IL-8、IL-6、TNF-α与FEV1%预计值的相关性。结果肺功能综合评估分级级别越高,其IL-8、IL-6和TNF-α的水平显著增高(p<0.05);COPD急性加重期及稳定期患者的IL-8、IL-6、TNF-α水平和FEV1%预计值水平均呈负相关(p<0.05)。结论老年AECOPD患者IL-8、IL-6和TNF-α水平和FEV1%预计值呈负相关,检测IL-8、IL-6和TNF-α的水平可反应出患者病情的严重程度,有助于临床评估患者的病情,指导临床治疗。     

The immunopathogenic and immunomodulatory effects of interleukin‐12 in periodontal disease

Interleukin 12 (IL‐12) is an inflammatory cytokine that promotes the response of the immune system. This cytokine has been implicated as a potent stimulator of several diseases characterized by inflammatory‐induced bone destruction, such as rheumatoid arthritis and periodontitis. Yet, the exact role of IL‐12 in the development and progress of periodontitis has not been clarified. Several studies have demonstrated a positive correlation between the level of IL‐12 and the severity of periodontal destruction. Deletion of IL‐12 in mice with periodontitis significantly suppressed the level of bone destruction. Interestingly, next to a role in modulating the pathogenesis, IL‐12 also has immunological‐regulatory properties. This cytokine induces expression of immunosuppressive molecules, such as indoleamine‐pyrrole 2,3‐dioxygenase (IDO). Thus, these findings suggest both negative and positive influences of IL‐12 in periodontal disease. It is currently proposed that the diversity of action of cytokines is a molecular key which regulates biological development and homeostasis. Accordingly, the actions of IL‐12 might be one of the mechanisms that regulate homeostasis of periodontal tissue during and following inflammation. Therefore, this article aims to review both destructive and protective functionalities of IL‐12 with an emphasis on periodontal disease.     

Anti-glycative and anti-inflammatory effects of protocatechuic acid in brain of mice treated by d-galactose

Protocatechuic acid (PCA) at 0.5%, 1% or 2% was supplied to d-galactose (DG) treated mice for 8 week. PCA intake at 2% increased its deposit in brain. DG treatment increased brain level of reactive oxygen species, protein carbonyl, carboxymethyllysine, pentosidine, sorbitol, fructose and methylglyoxal (P < 0.05). PCA intake, at 1% and 2%, lowered brain level of these parameters (P < 0.05). DG treatments enhanced activity and protein expression of aldose reductase (AR) and sorbitol dehydrogenase, as well as declined glyoxalase I (GLI) activity and protein expression (P < 0.05). PCA intake at 1% and 2% reduced activity and protein expression of AR (P < 0.05), and at 2% restored GLI activity and expression (P < 0.05). DG injection also elevated cyclooxygenase (COX)-2 activity and expression, and increased the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E₂ in brain (P < 0.05). PCA intake decreased these cytokines (P < 0.05), and at 1% and 2% suppressed COX-2 activity and expression (P < 0.05). PCA intake at 1% and 2% also lowered DG-induced elevation in activity, mRNA expression and protein production of nuclear factor kappa B p65 (P < 0.05). These findings suggest that the supplement of protocatechuic acid might be helpful for the prevention or alleviation of aging.     

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS₂ score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS₂ and CHA₂DS₂‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.     

IL-17 inhibition in axial spondyloarthritis: current and future perspectives

Introduction: Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication.

Areas covered: This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized.

Expert opinion: The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe.