Colloquium C016: The Mystery of the Relapse in MS ‐ the Interation of the Periferal and Central Immune System

Systemic inflammation, evoked by an infection or injury leads to the production of inflammatory mediators that communicate with the brain. This communication route involves further synthesis of inflammatory mediators in the brain, and this leads in turn to changes in metabolism and behaviour. There is evidence to show that resident cells of mononuclear phagocyte lineage are key players in this process. In an animal model of chronic neurodegeneration, murine prion disease, we have shown that there is an atypical inflammatory response dominated by the presence of activated perivascular macrophages and microglia. These cells synthesise minimal levels of proinflammatory cytokines. However, following asystemic inflammatory challenge mice with prion disease were challenged with endotoxin (LPS) or poly IC to mimic a systemic bacterial or viral infection. Following challenge, the mice with prion disease showed exaggerated sickness behaviour. This exaggerated sickness behaviour was associated with a dramatic switch in the cytokine profile in the brain from an anti-inflammatory to a proinflammatory profile. This switch in cytokine profile was also accompanied by an increase in the number of neurons undergoing apoptosis in the brains of animals with prion disease. These data lead to the hypothesis that systemic inflammation may affect both symptoms of chronic neurodegenerative disease and disease progression. Ongoing clinical studies in patients with Alzheimer’s disease support this hypothesis.