INTERLEUKIN-1-BETA INCREASES BASIC FIBROBLAST GROWTH-FACTOR MESSENGER-RNA EXPRESSION IN ADULT-RAT BRAIN AND ORGANOTYPIC HIPPOCAMPAL CULTURES

In situ hybridization was used to study the effect of IL-1 beta on aci dic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) mRNA expression in rat brain. Intraventricular injection of re combinant human IL-1 beta did not affect hybridization to aFGF mRNA bu t did induce significant and widespread increases in hybridization to bFGF mRNA. IL-1 beta induced increases in bFGF mRNA were bilaterally d istributed and appeared to correspond with the distribution of non-neu ronal cells. Thus, hybridization was increased in regions of both gray and white matter (e.g., corpus callosum), the ependymal lining of the third ventricle, and the pia matter. In hippocampus of IL-1 beta inje cted rats, hybridization was markedly increased in the molecular layer s but not significantly increased in the neuronal cell layers. Elevati ons in bFGF mRNA were transient, peaking at 8 h postinjection in most areas. To determine if IL-1 beta effects were independent of activatio n of the hypothalamo-pituitary-adrenal axis, and to compare the cellul ar localization of increases in bFGF mRNA expression induced by IL-1 b eta and bFGF, the regulation of bFGF expression was also studied in or ganotypic hippocampal slice cultures. Treatment of cultures with eithe r IL-1 beta or bFGF stimulated the same general distribution of increa ses in bFGF mRNA as seen after IL-1 beta treatment in vivo with an add itional effect on immature neurons within the hilar side of stratum gr anulosum; hybridization of bFGF mRNA was not increased in association with the more mature neurons of stratum pyramidale or stratum granulos um. Colocalization of bFGF cRNA hybridization with immunostaining for glial fibrillary acidic protein demonstrated that increases in bFGF mR NA induced both by IL-1 beta in vivo and in vitro and by bFGF in vitro were largely associated with astroglial cells. These findings suggest that IL-1 beta induction of bFGF contributes to the coactivation of t hese substances following various forms of insult to the CNS and initi ates a cascade of trophic interactions that regulates processes of gli al proliferation, neurotrophic factor expression, and neuroprotection.