MACROPHAGE ACTIVATION SYNDROME -ANALYSIS OF CLINICOPHYSIOLOGY AND ESTABLISHMENT OF THERAPY.
巨噬细胞激活综合征 - 临床生理学分析和治疗方法的建立。
基本信息
- 批准号:08670903
- 负责人:
- 金额:$ 1.41万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1996
- 资助国家:日本
- 起止时间:1996 至 1997
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Most of the proinflammatory cytokines such as TNF-alpha, interleukin (IL)-1, and IL-6 are the products of activated macrophages, which display the morphologic characteristics of hemophagocytosis in the bone marrow. Stephan et al.have suggested that the primary effector mechanism of this syndrome may indeed be ascribed to the overproduction of proinflammatory cytokines, especially TNF-alpha, by activated macrophages.The process of macrophage activation has yet to be investigated. The serum profile of M-CSF levels in our patients supports the idea that M-CSF may be the most potent stimulator of macrophages in the MAS,because M-CSF levels were closely linked to TNF-alpha levels and the clinical and laboratory parameters. The production of M-CSF by endothelial cells is promoted by IL-1 and TNF-alpha, and by T cells by IL-3. In turn, M-CSF primes the cells for subsequent TNF-alpha induction by other stimuli. Moreover, the hemophagocytic appearance of macrophages is usually seen in sinusoida … More l Kuoffer cells and splenic macrophages as well as bone marrow macrophages in virus-associated hemophagocytic syndrome (VAHS). This suggests that stroma cells or endothelial cells may play an important role in changing monocyte-macrophage functions. The activation of T cells in the VAHS also has been proven since increased serum levels of IL-2, soluble IL-2 receptor, and IFN-gamma, all of which are products of activated T cells, are detected. Taken together, it is possible to postulate that some predisposing factor(s) activates T cells to secrete IL-3 which stimulates back T cells and macrophages to produce M-CSF and IL-1/TNF-alpha, respectively, which then stimulates endothelial or stroma cells to produce more M-CSF.Eventually monocyte-macrophage functions are unduly influenced by the overproduced M-CSF.We cannot exclude the possibility that in our patients the administration of aspirin playd a critical role as a predisposing factor in the transition of systemic onset JRA to MAS,since viral infection and/or the administration of non-steroidal antiinflammatory drugs have been shown to be closely related to disease progression. The possible interaction between viral infection and aspirin needs further investigation.Laboratory findings indicated that our patients were at high risk of poor prognosis ; tissue damage was massive (LDH 20,880 and 4,647 IU/L,serum ferritin 64,313 and 55,324 ng/mL), blood coagulation was abnormal, and the bone marrow was suppressed. We therefore instituted plasmapheresis and administered dexamethasone and cyclosporine under the permission by their family and the ethical committee of our hospital. The introduction of this triple therapy was followed by a prompt improvement of the MAS accompanied by a decrease of serum TNF-alpha and M-CSF levels. For patients with VAHS,plasmapheresis and subsequent administration of VP16 and/or corticosteroids have been recommended. However, because of the possibility of the development of life-threatening infections due to the immunosuppressive effects of VP16 and due to its tumorigenic potential, we chose Cs A with the hope of suppressing T-cell activity. A satisfactory response was observed. One and half years in the first case and one year in the second case after the discontinuation of Cs A therapy the clinical and laboratory findings were stable. The children did not exhibit any clinical evidences of an exacerbation of systemic onset JRA.Thus, our observations provide evidence that M-CSF may be the promoting factor of TNF-alpha-cytokinemia which may induce MAS,and that Cs A along with plasmaexchange and dexamethasone therapy may be effective in the management of severe, life-threatening MAS. Less
大多数促炎细胞因子如tnf - α、白细胞介素(IL)-1、IL-6等都是巨噬细胞活化后的产物,在骨髓中表现出噬血的形态特征。Stephan等人认为,这种综合征的主要效应机制确实可能归因于活化的巨噬细胞过度产生促炎细胞因子,特别是tnf - α。巨噬细胞的活化过程还有待研究。我们患者的血清M-CSF水平支持M-CSF可能是MAS中巨噬细胞最有效的刺激物的观点,因为M-CSF水平与tnf - α水平以及临床和实验室参数密切相关。内皮细胞通过IL-1和tnf - α促进M-CSF的产生,T细胞通过IL-3促进M-CSF的产生。反过来,M-CSF为随后的tnf - α诱导细胞提供其他刺激。病毒相关性噬细胞综合征(VAHS)中,巨噬细胞表现为嗜血细胞样,多见于窦状窦,多见于脾巨噬细胞和骨髓巨噬细胞。这提示基质细胞或内皮细胞可能在单核-巨噬细胞功能的改变中起重要作用。由于检测到血清中IL-2、可溶性IL-2受体和ifn - γ水平升高,这些都是活化T细胞的产物,因此VAHS中T细胞的活化也得到了证实。综上所述,有可能假设某些诱发因素激活T细胞分泌IL-3, IL-3分别刺激T细胞和巨噬细胞产生M-CSF和IL-1/ tnf - α,然后刺激内皮细胞或基质细胞产生更多的M-CSF。最终单核巨噬细胞的功能受到过量产生的M-CSF的过度影响。由于病毒感染和/或非甾体抗炎药的使用已被证明与疾病进展密切相关,我们不能排除患者服用阿司匹林作为全身性JRA向MAS转变的易感因素发挥关键作用的可能性。病毒感染与阿司匹林之间可能的相互作用需要进一步研究。实验室结果表明,我们的患者预后不良的风险很高;组织损伤严重(LDH 20,880和4,647 IU/L,血清铁蛋白64,313和55,324 ng/mL),凝血异常,骨髓抑制。因此,我们在患者家属和我院伦理委员会的同意下进行血浆置换,并给予地塞米松和环孢素治疗。引入这种三联疗法后,MAS迅速改善,同时血清tnf - α和M-CSF水平下降。对于VAHS患者,建议血浆置换并随后给予VP16和/或皮质类固醇。然而,由于VP16的免疫抑制作用可能导致危及生命的感染,并且由于其致瘤性,我们选择了Cs A,希望能够抑制t细胞活性。观察到令人满意的反应。第一例停药1年半,第二例停药1年,临床和实验室检查结果均稳定。这些儿童没有表现出全身性发作的JRA加重的任何临床证据。因此,我们的观察结果提供了证据,证明M-CSF可能是tnf - α -细胞因子血症的促进因子,而tnf - α -细胞因子血症可能诱发MAS,并且Cs - A联合血浆交换和地塞米松治疗可能有效地治疗严重的、危及生命的MAS。少
项目成果
期刊论文数量(22)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mohri, Suzuki, Yokota: "Autoautibody inhibits binding ion Willbrond factor to glycoprotein Ib. Recognition site is located in the residue 512-673 of con Willbrand factor" Thrombosis and Haemostasis. 77. 760-766 (1997)
Mohri、Suzuki、Yokota:“Autoautibody 抑制 Willbrand 因子与糖蛋白 Ib 的结合。识别位点位于 Willbrand 因子的残基 512-673”血栓形成和止血。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
横田俊平,今川智之: "高サイトカイン血症〜その現況" Molecular Medicine. 33. 980-988 (1996)
Shunpei Yokota、Tomoyuki Imakawa:“高细胞因子血症 - 当前状态”分子医学 33. 980-988 (1996)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
今川智之,片倉樹、横田俊平: "マクロファージ活性化症候群の2症例" リウマチ(印刷中).
Tomoyuki Imakawa、Itsuki Katakura、Shunpei Yokota:“巨噬细胞活化综合征的两例”风湿病学(出版中)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Aihara, Mori, Yokota: "A pediatric case of polymyositis associated with Myaplaoma pneumoriae in peltion" Scand J Rhewuatol. 26. 480-481 (1997)
Aihara、Mori、Yokota:“一例与肺炎支原体相关的多发性肌炎儿科病例” Scand J Rhewuatol。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yokota, Iijima, et al,: "T-lymphotropic virus type 1 aveitis in a child." British Journal of Ophthalmology. 81. 1016- (1997)
Yokota, Iijima 等人:“儿童中的 T 淋巴细胞病毒 1 型燕窝炎”。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
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YOKOTA Shumpei其他文献
YOKOTA Shumpei的其他文献
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{{ truncateString('YOKOTA Shumpei', 18)}}的其他基金
Analysis and therapeutic research for growth impairment accompanied with chronic inflammatory syndrome of children as dysregulation of proinflammatory cytokines
促炎细胞因子失调所致儿童慢性炎症综合征生长障碍分析及治疗研究
- 批准号:
23591546 - 财政年份:2011
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
TLR/Nod proteins in infants from dysregulation Pathological analysis Cytokine Storm
婴儿中TLR/Nod蛋白失调引起的病理分析细胞因子风暴
- 批准号:
19390287 - 财政年份:2007
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Exhaustive analysis about juvenile idiopathic arthritis by using an anti-IL-6 receptor antibody
使用抗 IL-6 受体抗体对幼年特发性关节炎进行详尽分析
- 批准号:
16390305 - 财政年份:2004
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidation of pathogenesis of influenza-related encephalopathy using functional failure in rat glia cells
利用大鼠胶质细胞功能衰竭阐明流感相关脑病的发病机制
- 批准号:
14370249 - 财政年份:2002
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
PATHOPHYSIOLOGY OF INTRACRANIAL CYTOKINES IN INFLUENZA-ASSOCIATED ENCEPHALOPATHY
流感相关脑病中颅内细胞因子的病理生理学
- 批准号:
12470169 - 财政年份:2000
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
DISEASE-ACTIVITY MARKERS IN EPSTEIN-BARR VIRUS INFECTION AND ESTABLISHMENT OF CELL-LINE POSITIVE FOR EB VIRUS.
Epstein-Barr 病毒感染中的疾病活动标记和 EB 病毒阳性细胞系的建立。
- 批准号:
06670814 - 财政年份:1994
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Analysis of 1pr-dnT Cell Function in Sle-Prone Mouse, MRL/1pr.
易患 Sle 小鼠的 1pr-dnT 细胞功能分析,MRL/1pr。
- 批准号:
63570449 - 财政年份:1988
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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Proteomic Profiles and Novel Biomarkers in Juvenile Rheumatoid Arthritis
幼年类风湿关节炎的蛋白质组谱和新型生物标志物
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幼年类风湿关节炎的蛋白质组谱和新型生物标志物
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