Effect of peripheral inflammation on an inflammatory model of demyelination

CARINA FERRARI

Cancun

Congreso; FALAN Meeting-55Congress of Physiological Science; 2012

FALAN

Multiple sclerosis is a chronic inflammatory disease characterized by demyelination and remyelination events. Etiology of the disease is still not clear and therapeutic interventions fail in reducing disability or influencing the disease progression. Pro-inflammatory cytokine Interleukin-1beta (IL-1) is associated with a spectrum of neuroinflammatory processes in neurodegenerative diseases. We previously studied that the chronic expression of IL1 in the striatum, induced neutrophil infiltration, micro and astroglial activation and reversible demyelination. On the other hand, our lab and others recently demonstrated that a peripheral proinflammatory stimulus can exacerbate the damage produced by central stimulus in both Parkinson`s and prion disease models. However, few studies analyze the effect of peripheral infections in demyelinating diseases. The aim of this project is to analyze the effect of a peripheral inflammation on an ongoing inflammatory damage in the striatum. We used and adenovector expressing IL-1 (AdIL-1) to induce chronic expression in the striatum. Animals previously injected in the striatum with the AdIL-1, were injected endovenously with a pro-inflammatory stimuli 30 days after central stimulus. Animals injected with AdIL-1/AdIL-1 exhibited an exacerbation of both inflammatory and demyelinating response compared to AdIL-1/Adbgal. Animals AdIL-1/Adbgal exhibited a similar response to that observed in non-peripherally injected animals. Astroglia and microglia response were in accordance with the inflammatory response. In summary, pro-inflammatory stimuli exacerbate both inflammatory and demyelinating events. This response is accompanied by microglia and astroglia activation, and therefore increases the ongoing nervous tissue damage. Our data model provides data evidenced by the chronic expression of a unique proinflammatory cytokine, which allowed us to dissect the effect of this cytokine or its downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases and analyse the effect of peripheral inflammation on central damage.