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

Interleukin-1 beta (IL-1) is associated with a spectrum of inflammatory processes related to neurodegenerative disease. The effects of single-bolus injections of IL-1 into the CNS parenchyma give rise to neutrophil (PMN) recruitment, transient blood–brain barrier (BBB) breakdown, but no overt damage to CNS integrity. The effects of long-term IL-1 expression in brain parenchyma on CNS integrity have not been investigated. We used a recombinant adenovirus expressing IL-1 (AdIL-1) to examine the chronic effects of IL-1 expression in the CNS. Histochemical and immunohistochemical methods were used to characterize the immune response to an intrastriatal injection of 107 pfu of AdIL-1 and ELISA to quantified the IL-1 protein produced by the adenovector. IL-1 expression was detectable at 4, 8, 14, and 30 days postinjection. At days 1 and 2, some monocyte adherence was observed in the lumen of the vessels but between days 8 and 14 there was marked and restricted recruitment of PMNs, vasodilatation and breakdown of the BBB. Microglia and astrocyte activation was evident at days 2, 8 and 14. At days 8 and 14, disorganization of the nervous tissue, demyelination were observed. The number of neurons in the striatum was not affected by the treatment. At 30 days, the nervous tissue appeared normal with no signs of demyelination, infiltration or BBB breakdown. Thus, we show that chronic expression of IL-1 can damage CNS integrity, that IL-1 generates a restricted leukocyte recruitment profile in the CNS, and that there is no tachyphylaxis to chronic IL-1 expression