Viral Myocarditis Group Research Articles

Distinct different expression of Th17 and Th9 cells in coxsackie virus B3-induced mice viral myocarditis

BackgroundRecently, a new subset of CD4+T helper(Th) cell that predominantly secret cytokine interleukin-9(IL-9) is identified, termed Th9 cell. It has been reported to participate in tissue inflammation and autoimmune responses, and induce disease which differed from Th17 cells. Th17 cells have been shown to play a critical role in viral myocarditis (VMC), but whether Th9 cells are involved in the pathogenesis of VMC remains unclear.ResultsBALB/c mice were intraperitoneally (i.p) injected with coxsackie virus B3(CVB3) for establishing VMC models. Control mice were treated with phosphate-buffered saline i.p. On day 0,7,14,21,28,35,42 after injection, myocardial histopathological changes were evaluated by hematoxylin-eosin staining. Splenic Th17 and Th9 cells subsets were analyzed by flow cytometry. And cardiac IL-17, IL-9 mRNA were measured by semi-quantitative reverse transcription-PCR and nested PCR, respectively. Results showed the levels of Th17 cells and IL-17 mRNA obviously increased in VMC mice on 7 day after infection, peaked on day 28, and highly persisted to at least day 42 (p < 0.05). While the frequencies of Th9 cells and IL-9 mRNA showed no significant difference between VMC and control group throughout the course of the experiment(p > 0.05).ConclusionsIt was differentiated Th17 but not Th9 cells significantly elevated in the development of CVB3-induced VMC. The microenvironment of VMC seemed to contribute to the differentiation and proliferation of Th17 rather than Th9 cells. Our preliminary data implied Th9 cells could not protect against VMC nor promote the disease.

Expression and significance of TRAIL and its receptor DR5 in murine myocardium with acute viral myocarditis

Objective To deterine the expression of TNF-related apoptosis inducing ligand (TRAIL) and its receptor DR5 in murine myocardium with acute viral myocarditis(VM).Methods We builted the model of VM.Eight mice of the VM group and the normal control group were sacrificed on the 7th,10th,14th,21st,28th day after inoculation CVB3 virus.The myocardial histopathological scores were counted.The terminal reansferase-mediated dUPT-biotin nick end-labeling (TUNEL) assays was used to quantified apoptosis rate.The expression of TRAIL and DR5 protein and mRNA were determined by the method of immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR).Results The expression of TRAIL and DR5 protein and mRNA were found in myocardium of both the normal control group and the VM group.The expression of TRAIL protein of the VM group(14th) were significantly higher than which in the normal group at the same time and the VM group(7th)(F=9.17,P<0.01).The DR5 protein of the VM group(10th,14th,21st)were significantly higher than which in the normal group at the same time and the VM group(7th)(F=13.32,P<0.01).The expression of TRAIL and DR5 protein were positive correlated with the myocardial histopathological scores and the apoptosis rate.The expression of TRAIL mRNA of the VM group(10th) were significantly higher than which in the normal group at the same time and the VM group(7th)(F=10.86,P<0.01).The DR5 mRNA of the VM group(10th,14th)were significantly higher than which in the normal group at the same time and the VM group(7th)(F=22.75,P<0.01).Conclusion High characteristic expressions of protein/mRNA TRAIL and DR5 were observed in the myocardium of mice with VM.The level was positive correlationed with the account of pathology and the rate of apoptosis.The apoptosis induced by TRAIL and DR5 may participate in the pathophysiological processes of VM. Key words: Coxsackie virus; Myocarditis; Tunor necrosis factor related apoptosis inducing ligand; Death receptor 5; Apoptosis

Interleukin 17 level changes in different stages of Coxsackie virus-induced myocarditis in mice

Objective To investigate IL-17 and IL-23 levels change in Coxsackie virus-induced myocarditis in mice,aiming at effect of IL-17 in viral myocarditis.Methods A total of 100 male BALB/c mice,4 weeks old,including 80 in the viral myocarditis (VMC)group and 20 in the control group,were used.Mice in VMC group were peritoneally injected (PI)with Coxsackie virus B3(CVB3/Nancy).Mice were sacrificed at day 14,28,42 and 56 after PI.For different stages post infection,pathological changes of the mouse were observed,and IL-17 of heart by immunohistochemistry.Splenocytes were collected from the mice and restimulated with phytohemagglutinin (PHA)for 2 days in vitro.IL-17 mRNA and IL-23 mRNA of splenocytes were measured by RT-PCR and compared with those in the control.Results (1)IL-17 mRNA extracted from splenocytes increased at day 28 after PI as compared with that in the control and 14 days (both P＜0.01),and decreased at day 42 and 56.(2)All of the VMC group and control mice expressed IL-23 mRNA,but IL-23 mRNA level,which up-regulated at day 14,increased earlier than IL-17 mRNA,and continued to rise to a high level after that.(3)Heart IL-17 level which examined by integrate optical density also increased at day 28 of viral myocarditis in mouse as compared with that in the control and 14 days ( both P＜0.01).And the protein levels decreased at day 42 and 56 then.Conclusion The mRNA and protein levels of IL-17 were promoted in Coxsackie virus-induced myocarditis mice after 28 days.IL-23 mRNA expression was up-regulated also.This result suggested that Th17 subset is differentiated in chronic stage of viral myocarditis. Key words: Interleukin; Coxsackie virus; Myocarditis; Mice

The correlation between heart rate turbulence of pediatric viral myocarditis and other indexes

Objective To study the value of heart rate turbulence(HRT) of acute pediatric viral myocarditis (VMC) ,and the relationship between HRT and other indexes. Methods We randomly assigned 75 acute pediatric VMC and 77 health enfant those all received holter. We calculated the heart rate turbulence(To) and turbulence slope (Ts) respectively,and compared the difference between them. Simultaneously, record the number of ventricular pre-mature complex(VPC) ,whether with ventricular tachycardia(VT) and the SDNN index of HRV. Then we analyzed the association between them and To,Ts. Results The difference of To between pediatric VMC and control group is significant in statistics, as follows [ (1.47±2.03 ) %, (-0.78±2.55) %, P<0.01; (3.05±2.12) ms/RR, (8.82±3.42) ms/RR,P<0.01]. There are no correlation between To and the number of VPC. And the number of VPC is interrelated to Ts. To and Ts are not correlative with whether with VT and heart rate variability(HRV). Conclusions The HRT of pediatric VMC is significanty reduced,so HRT can be a new index that to evaluate the heart parasym-pathetic function state in pediatric VMC and it is independent from traditional HRV. Therefore we can evaluate the heart parasympathetic function state of the sufferers after analyzed their HRT. This technique can help to discover pathological changes of heart parasympathetic system in forepart and guide clinical therapy in time,and avoid heart ill event. Key words: Heart rate; Myocarditis; Ventricular premature complexs; Child