REPEATED PRO-INFLAMMATORY DEMYELINATING STIMULI MAY RESULT IN REDUCED INFLAMMATION AND DEMYELINATION

VERÓNICA MURTA, RODOLFO TARELLI, CARINA FERRARI, FERNANDO PITOSSI

Varadero, Cuba

Workshop; 1st International Workshop of Neuroimmunology; 2008

Sociedad Cubana de Farmacología

Patients in the relapsing phase of MS show high levels of IL-1â in the cerebrospinal fluid, and blockade of this cytokine reduces the severity of the disease. We have previously observed that chronic expression of IL-1â in the striatum produces reversible demyelination, blood-brain barrier breakdown and axonal damage, but no neurodegeneration. Most MS patients present relapsing-remitting episodes, and considering that remyelination is less efficient after every relapse, our hypothesis is that repeated pro-inflammatory stimulus in the brain could exacerbate demyelination in animals which had received a previous demyelinating stimulus. To contrast this hypothesis, we administered either adenoviral vectors expressing IL-1â (AdIL-1â) or unrelated inflammatory stimuli (LPS or PolyI:C). At different time points, we re-administered the AdIL-1 â in the striatum. We used â-Galactosidase (Adâ-gal) as a control of the AdIL-1â. Animals receiving pro-inflammatory stimuli in both opportunities had less inflammation and demyelination than animals receiving a unique pro-inflammatory stimulus. Additionally, a difference in the quality of the infiltrate was observed: animals which received repeated pro-inflammatory stimuli had a higher proportion of neutrophils. To asses the response of the tissue in different stages of the remyelinating process, we administered the second pro-inflammatory stimuli after 51 days. With this protocol, we observed less inflammation and demyelination than the earlier stimulus. Finally, we observed that the astrocytic and microglial activation followed the same pattern of the inflammation. In conclusion, contrary to our hypothesis we observed that a previous pro-inflammatory stimulus may reduce the inflammatory and demyelinating effect of a second pro-inflammatory stimulus, when administered in a 30 days interval.