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Content archived on 2024-05-14

Anti-inflammatory cytokines in neurological disease: Mechanisms and therapeutic potential

Objective

The overall objective of this project is to test the hypothesis that cell death in the central nervous system is critically dependent on the balance between pro-inflammatory cytokines such as interleukin-1, and anti-inflammatory cytokines such as the interleukin-1 receptor antagonist, interleukin-4, interleukin-10 and interleukin-13.

For this purpose, the participating laboratories will :
assess whether experimental insults which lead to brain damage modify the brain expression of anti-inflammatory cytokines in a regional and temporal manner;
determine the contribution of these anti-inflammatory cytokines to brain insults, by experimentally modifying expression and action of these molecules in well defined model systems;
investigate the way anti-inflammatory cytokines interfere with the synthesis and actions of interleukin-1 in the brain.

Using standardized reagents produced by a Centralized Facility, the participants will study the expression and action of anti-inflammatory cytokines in several animal models of brain inflammation, which differ by the severity, time course and cell types responsible for the local production of these molecules (brain resident cells or invading blood cells). These animal models include a model of acute non-immune brain inflammation (systemic administration of lipopolysaccharide), a model of acute brain trauma (lateral fluid percussion on the cortex), a model of chronic non-immune-mediated neurodegeneration (cerebellar mutant mice), and a model of chronic immune-mediated brain inflammation (the delayed-type hypersensitivity response to bacillus Calmette Guerin). For each of these models, standard animals and transgenic animals with an overexpression or a decreased expression of anti-inflammatory cytokines will be used. The investigation of the mechanisms of action of anti-inflammatory cytokines on the expression and action of pro-inflammatory cytokines will be carried out in vitro, using primary cultures of neurones, astrocytes and microglia.

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Programme(s)

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Topic(s)

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Call for proposal

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Funding Scheme

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CSC - Cost-sharing contracts

Coordinator

Institut National de la Santé et de la Recherche Médicale
EU contribution
No data
Address
Rue Camille Saint Saëns
33077 Bordeaux
France

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Participants (7)

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