Correlations between skin lesions induced by anti-tumor necrosis factor-α and selected cytokines in Crohn's disease patients

AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(TNF-α)therapy METHODS:A prospective study included 30 adult patients with CD of Caucasian origin(19 men and 11women;mean age±SD 32.0±8.6 years)during biological therapy with anti-TNF-αantibodies from January2012 to March 2013.Eighteen patients were treated with infliximab,seven with adalimumab and five withcertolizumab.Inclusion criteria were exacerbation of the underlying disease,Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies.Patients with a history of psoriasis,atopic dermatitis and other autoimmune skin lesions were excluded from the study.The control group consisted of 12 healthy subjects.A diagnostic survey was carried out,blood tests and careful skin examination were performed,and the serum levels of IL-17,IL-23 and IFN-γwere measured using an enzyme-linked immunosorbent assays technique.Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by antiTNF-αtherapy.RESULTS:Skin manifestations occurred in 18 of CD patients during the anti-TNF-αtherapy(60%),in the average time of 10.16±3.42 mo following the beginning of the 52-wk treatment cycle.Skin lesions observed in CD patients during biological therapy included psoriasiform lesions(44.4%),and eczema forms lesions(22.2%).In CD patients with drug induced skin lesions significantly higher levels of hemoglobin(13.3±1.5 g/dL vs 10.8±1.9 g/dL,P=0.018)and hematocrit(39.9%±4.5%vs 34.3%±5.4%,P=0.01),as well as a significantly lower level of platelets(268±62×103/μL vs 408±239×103/μL,P=0.046)was observed compared with CD patients without skin manifestations.The concentrations of IL-17A and IL-23in CD patients with skin lesions developed under antiTNF-αtherapy were significantly higher compared to those in patients without lesions(IL-17A:39.01±7.03pg/mL vs 25.71±4.90 pg/mL,P=0.00004;IL-23:408.78±94.13 pg/mL vs 312.15±76.24 pg/mL,P=0.00556).CONCLUSION:Skin lesions in CD patients during bio-logical therapy may result from significantly increased concentrations of IL-17A and IL-23,which are strongly associated with TNF-α/Th1 immune pathways.

冠心病微生物感染状况与血清3种炎症标志物的相关性研究

目的探讨冠心病患者肺炎衣原体(CPN)、幽门螺杆菌(Hp)、人类巨细胞病毒(HCMV)3种病原微生物的感染状况与3种血清炎症标志物[超敏C-反应蛋白(hs-CRP)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)]水平的相关性。方法选取2012年7月至2013年12月住院的冠心病患者105例作为冠心病组,同时选择同期住院非冠心病患者76例作为对照组。检测两组CPN、Hp、HCMV 3种微生物的IgG抗体,以及血清中hs-CRP、IL-6和TNF-α浓度。结果冠心病组CPN-IgG、Hp-IgG和HCMV-IgG单阳性、双阳性和三阳性的阳性率分别为33.3%、52.3%、78.1%、41.9%、13.3%,对照组阳性率则分别为14.5%、35.5%、63.2%、23.7%、2.6%,两组的相应阳性率比较差异有统计学意义(P<0.05)。CPN-IgG、Hp-IgG和HCMV-IgG阳性对患冠心病的危险度比值比分别为3.297、2.278、2.352,差异有统计学意义(P<0.05)。随着冠心病的病原体感染负荷增加,3种血清炎症标志物浓度亦增加,每组间差异有统计学意义(P<0.05)。结论冠心病患者存在CPN、Hp、HCMV 3种病原微生物的混合感染,长期反复慢性混合感染与冠心病关系密切,可诱导炎症标志物之间相互协同共同参与冠心病的发生、发展过程。感染性因素是冠心病的独立危险因素,对冠心病的诊断治疗有积极意义。

Effects of wind-dispelling drugs and deficiency-nourishing drugs of Houshiheisan compound prescription on astrocyte activation and inflammatory factor expression in the corpus striatum of cerebral ischemia rats

This study explored protective effects of Houshiheisan and its compound prescription of wind-dispelling drugs and deficiency-nourishing drugs on cerebral ischemia in terms of astrocyte activation and inflammatory factor expression.Results suggested that Houshiheisan lessened neuronal degeneration in the corpus striatum on the ischemic side of rats following cerebral ischemia/reperfusion injury,contributed to astrocyte activation and glial fibrillary acidic protein expression in the corpus striatum and decreased the levels of interleukin-2,interleukin-6, interleukin-1βand tumor necrosis factor-α.Factor analysis results demonstrated that deficiency-nourishing drugs were more beneficial in protecting neurons and upregulating glial fibrillary acidic protein expression than wind-dispelling drugs.However,wind-dispelling drugs were more effective in increasing the number of glial fibrillary acidic protein-positive cells and reducing inflammatory factor expression than deficiency-nourishing drugs.These indicate that different ingredients of Houshiheisan suppress cerebral ischemic injury by promoting astrocyte activation and diminishing inflammatory factor expression.

Induction of acute hepatic injury by endotoxin in mice

Objective: To investigate the changes of scavenger re-ceptor （SR） and CD14 in Kupffer cells in endotox-emia in order to uncover the mechanism of the liverto turn a defense organ into effector one in sepsis.Methods: Mouse models of endotoxemia of differentseverity were reproduced by injection of different do-ses of lipopolysaccharide （LPS） via the tail vein.The expression of SR and CD14 in the liver was as-sayed by immunohistochemistry and was subsequent-ly analyzed with an image analysis system. The levelsof TNF-α and IL-6 in liver tissue were determinedwith ELISA.Results: The expression of SR in the liver in the high-dose group was markedly decreased one hour afterinjection of LPS, and also in the low-dose group at 3hours. The expression of SR in the liver in the twogroups was shown to be progressively decreased withthe time prolonged. There was significant differencein average optical density （OD） values of SR be-tween the two groups. The expression of CD14 in thetwo groups was shown to be significantly increasedone hour after injection of LPS, and more signifi-cantly with the time prolonged. But there was no sig-nificant difference in OD values of CD14 between thetwo groups. The contents of intrahepatic proinflam-matory mediators TNF-α, IL-6, ALT and TBILwere significantly increased after injection of LPS.Correlation analysis revealed that the changes ofTNF-α, IL-6, ALT, and TBIL were negatively cor-related with the expression of SR, and positively withthe expression of CD14.Conclusion: The up-regnlation of CD14 expressionand down-regulation of SR expression on Kupffercells might be one of the important mechanisms forthe conversion of Kupffer cells from immune defen-sive to inflammatory response cells in acute hepaticinjury.

Differential mRNA Expression of <i>COX</i>-2 and Proinflammatory Mediators in Patients with Rotator Cuff Tears and Osteoarthritis of the Hip

Purpose: Bursal inflammation is thought to be a major cause of pain in degenerative rotator cuff tears (RCTs). While the expression of proinflammatory mediators, such as COX-2, TNF-α, IL-1β, and IL-6, is crucial for the pathophysiology of osteoarthritis (OA), their role in degenerative RCTs remains unknown. The aim of this study was to determine the expression of COX-2 and proinflammatory mediators in the development of RCT-induced pain by comparing their levels in patients with hip OA or RCTs. Methods: We included samples obtained from 31 shoulders of 31 patients with RCTs and samples from 30 hips of 27 patients with hip OA. The mRNA levels of COX-2, TNF-α, IL-1β, and IL-6 were determined using RT-PCR, and were compared between the subacromial bursa and hip joints. We also analyzed IL-1β-induced COX-2 expression in the subacromial bursa and synovial blast of the hip. Results: COX-2, IL-1β, and IL-6 expression levels were significantly lower in the subacromial bursa of RCTs than in hip OA samples, while no significant difference was observed for TNF-α. No significant difference in the fold increase was observed between subacromial bursa and hip OA samples, even though IL-1β-induced COX-2 expression increased in both samples. Conclusion: Our findings suggest that the main mechanism underlying pain development differs between patients with RCTs and those with hip OA.

消融稳斑胶囊对动脉粥样硬化大鼠血管内皮细胞AMPK蛋白及血清TNF-α、IL-6、CRP表达的影响

目的:观察消融稳斑胶囊对动脉粥样硬化大鼠血管内皮细胞AMP激活蛋白激酶(AMP-activated protein kinase,AMPK)蛋白表达及血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、C反应蛋白(C-creactive protein,CRP)表达的影响,并探讨消融稳斑胶囊改善不稳定心绞痛的分子机制。方法:48只Wistar大鼠,随机分为空白组、模型组、瑞舒伐他汀组及消融稳斑胶囊组。观察大鼠给药前后IL-6、TNF-α、CRP等炎性因子的浓度,并采用Western blot方法测定大鼠血管内皮细胞的AMPK蛋白表达量。结果:消融稳斑胶囊能明显降低血清TNF-α、CRP水平,并与瑞舒伐他汀组比较,差异有统计学意义(P<0.05);消融稳斑胶囊能明显降低血清IL-6水平,并与瑞舒伐他汀效果相当;模型组AMPK表达明显高于空白组(P<0.01);与模型组比较,瑞舒伐他汀组、消融稳斑胶囊组能明显降低AMPK表达(P<0.01)。结论:消融稳斑胶囊可以降低动脉粥样硬化大鼠的血清炎症因子水平,同时增加血管内皮细胞AMPK蛋白表达。

Anti-aging and anti-carcinogenic effects of 1α,25-dihyroxyvitamin D_(3) on skin

Photoaging and carcinogenesis are facilitated by oxidative stress,inflammation,angiogenesis,and extracellular matrix(ECM)remodeling.Oxidative effects include DNA damage,membrane oxidation,lipid peroxidation,and alterations in the expression of p53 and antioxidant enzymes.The inflammatory and angiogenesis mediators include interleukin-1,tumor necrosis factor-α,interleukin-8,transforming growth factor-β,and vascular endothelial growth factor.ECM remodeling includes alterations in the expression and organization of collagen,elastin,matrix metalloproteinases,and elastase.1α,25-dihydroxy-vitamin D_(3) has antioxidant,anti-inflammatory,and ECM regulatory properties,and can counteract the processes that facilitate photoaging and carcinogenesis.This review provides an overview of the beneficial effects of vitamin D supplementation at a molecular level,followed by a brief discussion regarding its use as a supplement.