The effects of adenoviral-mediated chronic expression of IL-1?Ò in the striatum

FERRARI C; CHERTOFF M; DI PAOLO N; MURARO N; DEPINO A; ANTHONY DF; PITOSSI F

Orlando

Congreso; 32nd Annual Meeting of the Society for Neuroscience; 2002

Society for Neuroscience

Expression of Interleukin-1 beta (IL-1β) is associated with a spectrum of neuropathologies. Prior studies have analyzed the effects of single-bolus injections of IL-1β into the CNS parenchyma where it gives rise to neutrophil (PMN) recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. The effects of long-term IL-1β expression in brain parenchyma on CNS integrity have not been investigated. We used a recombinant adenovirus expressing IL-1β (AdIL-1) to examine the chronic effects of IL-1β expression in the CNS. Histochemical and IHC were used to characterize the immune response to an intrastriatal injection of 10e7 pfu/μl of AdIL-1 and sqRT-PCR to analyze the induction of cytokines. IL-1β expression was detectable at 4, 8, 14, and 21 days, but not at 30 days. Initally, some monocyte adherence was observed in the lumen of the vessels (d1&d2), but between d8 and d14 there was marked and restricted recruitment of PMNs and breakdown of the BBB. Microglia and astrocyte activation was evident at d2, d8 and d14. At d8 and d14, disorganization of the nervous tissue, demyelination and neurodegeneration were observed. At d30 the tissue was appeared normal with no signs of demyelination, infiltration or BBB breakdown. IL-2 was transiently expressed, d2, and IL-1ra expression was most marked at d8 and d21. Thus we show that chronic expression of IL-1β can damage CNS integrity, that IL-1β generates a restricted leukocyte recruitment profile in the CNS, and that there is no tachyphylaxis to chronic IL-1β expression.