PSYCHONEUROIMMUNOLOGY--INNERVATION & AUTOIMMUNE DISEASE
心理神经免疫学--神经支配
基本信息
- 批准号:2033909
- 负责人:
- 金额:$ 15.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-09-30 至 1997-10-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Extensive studies from our laboratories have shown the presence of
noradrenergic (NA) and substance P (SP) innervation of lymphoid organs.
Numerous studies have reported that these neuro-transmitters can modulate
immune functions. Conversely, Besedovsky and coworkers have shown that an
immune response can alter neurotransmitter levels in reacting target
lymphoid organs. We, and others, have evidence to support a role for NA
and SP innervation of lymphoid organs in age-related immuno-suppression,
and a variety of autoimmune disease models, such as experimental adjuvant-
induced arthritis (EA). Both clinical studies of rheumatoid arthritis (RA)
and experimental evidence of EA indicate involvement of NA and SP
innervation in the pathophysiology of this disease. Clinical findings
which are consistent with nervous system involvement in RA include: (1) a
symmetric distribution of synovitis; (2) hemiplegic patients who later
develop RA are spared the inflammatory process in joints on the paretic
side; and (3) onset and exacerbation of the disease are often preceded by
psychological trauma. It is well documented that NE and SP can modulate
chronic inflammatory response and degree of destruction in the joints
associated with RA and EA. Many experimental studies have employed
systemic methods of denervation to demonstrate a role for these
neurotransmitter systems, which would denervate several potential sites of
action for these transmitters, including the joint, primary and secondary
lymphoid organs, and central outflow to autonomic ganglia. Recently our
laboratory has revealed that SP innervation of draining lymph nodes (LNs)
is necessary for full expression of EA. This proposal further investigates
the influence of NA and SP innervation of draining LNs in development and
severity of EA in Lewis rats. Specifically, we propose to examine: (1)
the effect of regional denervation of SP or NA innervation of popliteal and
inguinal LNs on the expression of EA using chemical denervation,
neurochemical analysis of SP and NE and assessing the time of onset,
progression, and severity of EA in Lewis rats; and (2) the effect of EA and
local inflammatory responses on NA and SP innervation of draining LNs, and
subsequent immune responses in LNs, using double-label immunocytochemistry,
neurochemical analysis of SP and NE, and beta-adrenoceptor and SP receptor
binding assays. Functional studies will examine immuno-responsiveness of
EA rats for correlation with neurochemical and anatomical measures of SP
and NA innervation. These studies will provide a better understanding of
the feedback circuitry involved in the development of EA, the functional
consequences of EA in secondary lymphoid organs, and the role of SP and NA
innervation during this disease processes. The ultimate significance of
such studies lies in use of in vivo pharmacologic manipulation of
neurotransmitters or neuromodulators that innervate lymphoid tissue, as a
means of altering immune function and host defense, and the possible
implications for development of therapeutive approaches for intervention of
autoimmune diseases, such as RA.
我们实验室的广泛研究表明
甲肾上腺素能(Na)和P(SP)淋巴器官的神经支配。
许多研究报告说,这些神经递质可以调节
免疫功能。 相反,贝斯多夫斯基和同事表明
免疫反应可以改变反应靶点的神经递质水平
淋巴器官。 我们和其他人都有证据支持NA的角色
淋巴机器人在与年龄有关的免疫抑制中的SP神经支配,
以及多种自身免疫性疾病模型,例如实验辅助 -
诱导关节炎(EA)。 类风湿关节炎(RA)的两项临床研究
EA的实验证据表明NA和SP的参与
这种疾病的病理生理学神经。 临床发现
与神经系统参与RA一致的包括:(1)a
滑膜炎的对称分布; (2)偏瘫患者后来
发育ra在偏to的关节中幸免于炎症过程
边; (3)疾病的发作和加剧通常是在
心理创伤。 有充分的文献证明NE和SP可以调节
慢性炎症反应和关节破坏程度
与RA和EA相关。 许多实验研究已经采用
全身去神经的方法来证明这些作用
神经递质系统,它将取消几个潜在地点
这些发射器的作用,包括关节,主要和次级
淋巴器官,中心流向自主神经节。 最近我们的
实验室表明,淋巴结淋巴结(LNS)的SP神经
对于完全表达EA是必要的。 该提案进一步调查了
NA和SP神经在发育中排水LN的影响以及
刘易斯大鼠EA的严重程度。 具体而言,我们建议检查:(1)
popliteal和
使用化学神经保护的腹股沟LN在EA表达上,
SP和NE的神经化学分析,并评估发作时间
刘易斯大鼠的EA的进展和严重程度; (2)EA和EA的影响
局部炎症反应对排水LN的Na和SP神经支配,以及
随后使用双标签免疫细胞化学的LN中的免疫反应,
SP和NE的神经化学分析,以及β-肾上腺素受体和SP受体
绑定测定。 功能研究将检查的免疫反应性
EA大鼠与SP的神经化学和解剖学度量相关
和NA神经。 这些研究将提供更好的理解
EA的发展,功能性的反馈电路
EA在继发性淋巴机构中的后果以及SP和Na的作用
在这种疾病过程中的神经。 最终意义的
这样的研究在于使用体内药理操作
神经递质的神经递质或神经调节剂,将淋巴组织神经化,作为A
改变免疫功能和宿主防御的手段,并可能
对开发治疗方法的影响
自身免疫性疾病,例如RA。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Local application of capsaicin into the draining lymph nodes attenuates expression of adjuvant-induced arthritis.
将辣椒素局部应用到引流淋巴结可减弱佐剂诱导的关节炎的表达。
- DOI:10.1159/000026429
- 发表时间:2000
- 期刊:
- 影响因子:2.4
- 作者:Lorton,D;Lubahn,C;Engan,C;Schaller,J;Felten,DL;Bellinger,DL
- 通讯作者:Bellinger,DL
共 1 条
- 1
DIANNE LORTON的其他基金
Human Spinal Cord Glial Cytokines and Chronic Pain
人脊髓神经胶质细胞因子和慢性疼痛
- 批准号:71252907125290
- 财政年份:2006
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
Human Spinal Cord Glial Cytokines and Chronic Pain
人脊髓神经胶质细胞因子和慢性疼痛
- 批准号:72911057291105
- 财政年份:2006
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
GLIAL ANTIPROLIFERATIVE FACTOR AS A TUMOROSTATIC AGENT
胶质细胞抗增殖因子作为肿瘤抑制剂
- 批准号:34929053492905
- 财政年份:1992
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
PSYCHONEUROIMMUNOLOGY--INNERVATION & AUTOIMMUNE DISEASE
心理神经免疫学--神经支配
- 批准号:22486002248600
- 财政年份:1991
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
PSYCHONEUROIMMUNOLOGY:INNERVATION AND AUTOIMMUNE DISEASE
心理神经免疫学:神经支配和自身免疫性疾病
- 批准号:34758563475856
- 财政年份:1991
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
PSYCHONEUROIMMUNOLOGY--INNERVATION & AUTOIMMUNE DISEASE
心理神经免疫学--神经支配
- 批准号:22485992248599
- 财政年份:1991
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
PSYCHONEUROIMMUNOLOGY:INNERVATION AND AUTOIMMUNE DISEASE
心理神经免疫学:神经支配和自身免疫性疾病
- 批准号:34758573475857
- 财政年份:1991
- 资助金额:$ 15.27万$ 15.27万
- 项目类别:
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