Macrophage Inactivation in Sepsis after Shock or Trauma
Macrophage Inactivation in Sepsis after Shock or Trauma
批准号:
7933295
负责人:
Kevin J Tracey
金额:
$27.81万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-30 至 2012-08-31
关键词:
AblationAddressAgonistAnatomyAnimal ModelAnti-Inflammatory AgentsAnti-inflammatoryArthritisBiologicalBrainCellsCholinergic AgonistsColitisCytokine SuppressionDevelopmentDiseaseElectric StimulationEndotoxemiaEndotoxinsFunctional disorderGrantHMGB1 geneHeart RateHemorrhagic ShockHost DefenseHourImmune responseImmune systemImmunohistochemistryIn SituInfectionInflammatoryIschemiaKnowledgeLaboratoriesMeasurementMediatingModelingMolecularMuscarinicsNatureNerveNervous system structureNeurotransmitter ReceptorOperative Surgical ProceduresOrganPathway interactionsPatientsPeripheralProductionRecording of previous eventsReflex actionReperfusion TherapyResearchResearch DesignResearch PersonnelReticuloendothelial SystemRoleSepsisShockSignal TransductionSpleenStructure of splenic veinSurgical InjuriesSystemTNF geneTestingTherapeuticTherapeutic EffectTimeTraumaUpper armVagus nerve structurebasebrain pathwaycholinergiccholinergic neuronclinically relevantcytokineintraperitonealmacrophagemind controlneuromechanismneurophysiologyneurotransmitter releasenovelpre-clinicalpreclinical studyprogramsreceptorrelating to nervous systemresearch studyresponseresponse to injurytherapy designvagus nerve stimulation
中文摘要
自1998年成立以来,该基金的主要目标一直是阐明生物机制
英文摘要
The principal objective of this grant, since its inception in 1998, has been to elucidate biological mechanisms
that regulate the immune response to injury and infection. This led to the discovery of a neurophysiological
mechanism by which the brain controls the peripheral immune system through the vagus nerve, the principle
cholinergic nerve that connects the brain to the organs of the reticuloendothelial system. This discovery
opened a new field of research, now termed "The Inflammatory Reflex" (Tracey KJ. The inflammatory reflex.
Nature. 2002 Dec 19-26;420:853-9). Preclinical studies in animals models of sepsis, endotoxemia,
ischemia-reperfusion, trauma, and shock have revealed that this pathway may be exploited to develop new
therapies to treat patients with these and other diseases caused by cytokine overproduction. While these
studies have clearly demonstrated a major role for this pathway in controlling cytokine release, there remain
important unanswered questions about cellular, molecular, and neural mechanisms. In Specific Aim 1 we will
test the hypothesis that the mechanism of cytokine suppression by the cholinergic anti-inflammatory pathway
requires cholinergic neural input to cytokine producing cells in spleen. In Specific Aim 2 we will test the
hypothesis that activation of cholinergic mechanisms in brain regulates cytokine release during endotoxemia,
and in a standardized preclinical therapeutic model of CLP sepsis. These studies are essential to move the
field forward. The concept of applying a classical neurophysiological study design (based on either
electrically stimulating the vagus nerve or administering a selective neurotransmitter receptor agonist to
activate a brain network) to specifically dissect a functional pathway for brain modulation of the immune
response is singular, novel, and likely to provide significant new information about the nervous system
control of the immune response. The Tracey laboratory, which has led the development of this field, is now
particularly well suited to do these studies.
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会议论文
Molecular basis of bioelectronic medicine
-
批准号:10394188
-
项目类别:
-
资助金额:$75.38万
-
财政年份:2016
-
负责人:Kevin J Tracey
-
依托单位:
Molecular basis of bioelectronic medicine
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批准号:10614430
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项目类别:
-
资助金额:$75.38万
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财政年份:2016
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负责人:Kevin J Tracey
-
依托单位:
Molecular Basis of Bioelectronic Medicine
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批准号:9071799
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项目类别:
-
资助金额:$51.42万
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财政年份:2016
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负责人:Kevin J Tracey
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依托单位:
Molecular Basis of Bioelectronic Medicine
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批准号:9473066
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项目类别:
-
资助金额:$71.78万
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财政年份:2016
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负责人:Kevin J Tracey
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依托单位:
Molecular Basis of Bioelectronic Medicine
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批准号:9906903
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项目类别:
-
资助金额:$71.78万
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财政年份:2016
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负责人:Kevin J Tracey
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依托单位:
PKR mediated inflammasome activation and pyroptosis in sepsis
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批准号:8496322
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项目类别:
-
资助金额:$32.02万
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财政年份:2014
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负责人:Kevin J Tracey
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依托单位:
Central cholinergic regulation of inflammation
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批准号:8338817
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项目类别:
-
资助金额:$28.22万
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财政年份:2011
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负责人:Kevin J Tracey
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依托单位:
Central cholinergic regulation of inflammation
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批准号:8042116
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项目类别:
-
资助金额:$28.22万
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财政年份:2011
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负责人:Kevin J Tracey
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依托单位:
VAGUS NERVE STIMULATION IN RHEUMATOID ARTHRITIS (VANSRA)
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批准号:7951920
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项目类别:
-
资助金额:$0.29万
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财政年份:2009
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负责人:Kevin J Tracey
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依托单位:
CHOLINERGIC MODULATION OF CYTOKINE SYNTHESIS IN SEPSIS SURVIVORS
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批准号:7719247
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项目类别:
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资助金额:$0.28万
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财政年份:2008
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负责人:Kevin J Tracey
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依托单位:
EFFECT OF AURICULAR VAGUS NERVE STIMULATION ON HEART RATE VARIABILITY IN HEALTHY
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批准号:7719287
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项目类别:
-
资助金额:$1.29万
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财政年份:2008
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负责人:Kevin J Tracey
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依托单位:
VAGUS NERVE STIMULATION IN RHEUMATOID ARTHRITIS (VANSRA)
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批准号:7719270
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项目类别:
-
资助金额:$11.23万
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财政年份:2008
-
负责人:Kevin J Tracey
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依托单位:
CHOLINERGIC MODULATION OF RHEUMATOID ARTHRITIS
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批准号:7608240
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项目类别:
-
资助金额:$3.86万
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财政年份:2007
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负责人:Kevin J Tracey
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依托单位:
THE REMOVAL OF CIRCULATING TOXINS DURING HEMODIALYSIS
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批准号:7608260
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项目类别:
-
资助金额:$0.24万
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财政年份:2007
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负责人:Kevin J Tracey
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依托单位:
CHOLINERGIC MODULATION OF CYTOKINE SYNTHESIS IN SEPSIS SURVIVORS
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批准号:7608235
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项目类别:
-
资助金额:$1.52万
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财政年份:2007
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负责人:Kevin J Tracey
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依托单位:
VAGUS NERVE STIMULATION IN RHEUMATOID ARTHRITIS (VANSRA)
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批准号:7608268
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项目类别:
-
资助金额:$1.56万
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财政年份:2007
-
负责人:Kevin J Tracey
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依托单位:
CHOLINERGIC MODULATION OF CYTOKINE SYNTHESIS IN SEPSIS SURVIVORS
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批准号:7377118
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项目类别:
-
资助金额:$5.37万
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财政年份:2006
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负责人:Kevin J Tracey
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依托单位:
CHOLINERGIC MODULATION OF RHEUMATOID ARTHRITIS
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批准号:7377124
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项目类别:
-
资助金额:$7.02万
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财政年份:2006
-
负责人:Kevin J Tracey
-
依托单位:
THE REMOVAL OF CIRCULATING TOXINS DURING HEMODIALYSIS
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批准号:7377146
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项目类别:
-
资助金额:$0.14万
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财政年份:2006
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负责人:Kevin J Tracey
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依托单位:
CHOLINERGIC MODULATION OF CYTOKINE SYNTHESIS IN SEPSIS SURVIVORS
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批准号:7203198
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项目类别:
-
资助金额:$1.57万
-
财政年份:2005
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负责人:Kevin J Tracey
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依托单位:
海外基金