Spatiotemporal effects of chronic expression of IL-1beta in the striatum

MARIELA CHERTOFF; FERRARI, CARINA; AMAICHA MARA DEPINO; PITOSSI, FERNANDO

Congreso; XXXVIII Reunión anual de investigación en Bioquímica y Biología molecular; 2002

SAIB

Interleukin-1 beta (IL-1b) is a proinflammatory cytokine associated with pathological events in the central nervous system. Moreover, IL-1b exacerbates ischemic, excitotoxic and traumatic brain injury.  Previous studies analyzed the effects of a single injection of IL-1b but no data were available considering the long-term effects of IL-1b in the brain parenchima. In the present study we analyzed the effects of chronic expression of IL-1b in rats striatum using a recombinant adenovirus expressing IL-1b (AdIL-1b). We used histological and immunohistochemical techniques to characterize the inmune response to intrastriatal injection of 10e7 pfu of AdIL-1b and SQRT-PCR to analyze the induction of cytokines. During the first two days after injection, monocyte recruitment was observed in the lumen of the vessels. The maximum recruitment of polimorphonuclear neutrophils and breakdown of the blood brain barrier were observed between 8 and 14 days, decreasing thereafter and dissapearing at 30 days. At 8 and 14 days, we could observe desorganization of the nervous tissue and demyielinization of the fibers of the striatum. Concomitantly, we found IL-1b mRNA expression in the ipsilateral striatum at 4 and 21 days postinjection. IL-1ra mRNA expression exhibited a maximum in the ipsilateral striatum at 8 and 21 days. TNF-a was only detected between 4 and 14 days. These results suggest a multiple role for the cytokine IL-1b. It is involved in the inflammatory response and demyelinization, while it also has a role in the posterior remyelinization and tissue repair.