BACKGROUND Brain tissue injury in stroke patients involves inflammation around the infarction lesion or hematoma,which is an important reason for disease deterioration and can result in a poor prognosis.The meta-analy...BACKGROUND Brain tissue injury in stroke patients involves inflammation around the infarction lesion or hematoma,which is an important reason for disease deterioration and can result in a poor prognosis.The meta-analysis of animal experiments has concluded that fingolimod could treat stroke in animal models by effectively reducing lymphocyte infiltration.However,no evidence-based efficacy and safety evaluation of fingolimod in stroke patients is currently available.AIM To determine whether fingolimod could promote reduction of infarction lesion or hematoma and improve neurological prognosis in stroke patients.METHODS Data extracted for treatment effect included count of T-lymphocytes with cluster of differentiation 8 expression(CD8^(+)T cells,×106/mL),lesion volume(infarction or hematoma,mL),and modified Barthel indexes.Data extracted for safety was risk ratio(RR).Overall standard mean difference(SMD)with its 95%confidence interval(95%CI)and pooled effect with its 95%CI were calculated with a fixedeffects model.I-square(I^(2))was used to test the heterogeneity.Funnel plot symmetry and Egger's regression were used to evaluate publication bias.RESULTS Four high-quality randomized controlled trials were included.There was a significant difference in CD8^(+)T cell count(I^(2)=0,overall SMD=-3.59,95%CI:-4.37-2.80,P=0.737)and modified Barthel index(I^(2)=0,overall SMD=2.42,95%CI:1.63-3.21,P=0.290)between the fingolimod and control groups.However,there was no significant difference in lesion volume(I^(2)=10.6%,overall SMD=-0.17,95%CI:-0.75-0.42,P=0.917),fever(pooled RR=0.93,95%CI:0.97-2.32,P=0.864),suspected lung infection(pooled RR=0.90,95%CI:0.33-2.43,P=0.876),or any adverse events occurring at least once(pooled RR=0.82,95%CI:0.36-1.87,P=0.995)between the fingolimod and control groups.There was no publication bias.All of the results were stable as revealed by sensitivity analysis.CONCLUSION Fingolimod improves neurological function in stroke patients without promotion of lesion absorption.Taking fingolimod orally(0.5 mg/d,3 consecutive days)is safe except for patients with rare severe adverse events.展开更多
Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated tha...Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.展开更多
Multiple sclerosis(MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acut...Multiple sclerosis(MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.展开更多
文摘BACKGROUND Brain tissue injury in stroke patients involves inflammation around the infarction lesion or hematoma,which is an important reason for disease deterioration and can result in a poor prognosis.The meta-analysis of animal experiments has concluded that fingolimod could treat stroke in animal models by effectively reducing lymphocyte infiltration.However,no evidence-based efficacy and safety evaluation of fingolimod in stroke patients is currently available.AIM To determine whether fingolimod could promote reduction of infarction lesion or hematoma and improve neurological prognosis in stroke patients.METHODS Data extracted for treatment effect included count of T-lymphocytes with cluster of differentiation 8 expression(CD8^(+)T cells,×106/mL),lesion volume(infarction or hematoma,mL),and modified Barthel indexes.Data extracted for safety was risk ratio(RR).Overall standard mean difference(SMD)with its 95%confidence interval(95%CI)and pooled effect with its 95%CI were calculated with a fixedeffects model.I-square(I^(2))was used to test the heterogeneity.Funnel plot symmetry and Egger's regression were used to evaluate publication bias.RESULTS Four high-quality randomized controlled trials were included.There was a significant difference in CD8^(+)T cell count(I^(2)=0,overall SMD=-3.59,95%CI:-4.37-2.80,P=0.737)and modified Barthel index(I^(2)=0,overall SMD=2.42,95%CI:1.63-3.21,P=0.290)between the fingolimod and control groups.However,there was no significant difference in lesion volume(I^(2)=10.6%,overall SMD=-0.17,95%CI:-0.75-0.42,P=0.917),fever(pooled RR=0.93,95%CI:0.97-2.32,P=0.864),suspected lung infection(pooled RR=0.90,95%CI:0.33-2.43,P=0.876),or any adverse events occurring at least once(pooled RR=0.82,95%CI:0.36-1.87,P=0.995)between the fingolimod and control groups.There was no publication bias.All of the results were stable as revealed by sensitivity analysis.CONCLUSION Fingolimod improves neurological function in stroke patients without promotion of lesion absorption.Taking fingolimod orally(0.5 mg/d,3 consecutive days)is safe except for patients with rare severe adverse events.
基金supported by the National Basic Research Development Program of China (2013CB966900)the National Natural Science Foundation of China (81241144, 81371372)the National Key Clinical Specialty Construction Program of China
文摘Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.
文摘目的探讨芬戈莫德(fingolimod,FTY720)对试验性自身免疫性脑脊髓炎(EAE)小鼠脑组织中一氧化氮(NO)含量和诱导型一氧化氮合酶(i NOS)表达的影响。方法 48只雌性C57BL/6小鼠随机平均分为3组,EAE组运用MOG35-55构建EAE小鼠模型;CFA组由生理盐水代替MOG35-55构建模型;FTY720干预组在EAE基础上给予FTY720腹腔注射,CFA组、EAE组给予生理盐水腹腔注射。HE染色和LBF染色观察炎症情况和脱髓鞘情况,ELLISA检测小鼠脑组织中的NO含量,RT-PCR检测的诱导型一氧化氮合酶(i NOS)mRNA表达。结果 FTY720组EAE小鼠较EAE组临床症状减轻,炎症程度和脱髓鞘程度减轻(P<0.05)。FTY720组小鼠脑组织NO含量较EAE组降低(P<0.05),i NOS mRNA表达量降低(P<0.05)。结论 FTY720能抑制EAE小鼠脑组织中i NOS mRNA表达,从而减少NO含量。
文摘Multiple sclerosis(MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.
