Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.     

HBV感染免疫耐受期孕妇分娩前后 临床指标及细胞因子水平变化特征

[摘要]　目的　分析HBV感染免疫耐受期孕妇分娩前后临床指标及细胞因子水平的变化规律，比较分娩后不同ALT水平组孕妇血清细胞因子水平差异。方法　选择2015年1月—2017年12月就诊于首都医科大学附属北京佑安医院的HBV感染免疫耐受期孕妇52例，妊娠28周给予替比夫定（telbivudine, LdT）抗病毒干预，分别于LdT干预前（基线）、分娩前（2周）及分娩后（6周）进行生化、血清学及病毒学检测，同步留取相应时间点外周血标本进行细胞因子检测，并分析分娩前后临床指标及细胞因子水平的变化特征。结果　52例患者分娩后6周ALT水平均值明显高于LdT干预前和分娩前，其中ALT≥2倍正常值上限（upper limit of normal, ULN）者达28.8%（15/52例）；与LdT干预前相比，分娩前HBV DNA水平显著下降，平均降幅达（3.68±0.79） lg IU/ml；HBsAg和HBeAg水平在分娩前后无明显变化。与分娩后ALT＜2倍ULN组相比，ALT≥2倍ULN组的IFN-γ水平在LdT干预前呈低水平表达，分娩后呈高水平表达，差异均有统计学意义（Z=2.284，P=0.022；Z=2.223，P=0.026）；2组间IL-2、IL-4、IL-6、IL-10、TNF-α在LdT干预前、分娩前及分娩后均无明显差异。结论　HBV感染免疫耐受期孕妇分娩后部分患者ALT明显升高，结合分娩前后细胞因子的动态变化，提示分娩后可能出现免疫功能增强并打破机体对HBV的免疫耐受，这或许有利于分娩后的抗病毒治疗，但仍须要进一步深入的研究。