RECIPROCAL CONTROL OF INFLAMMATORY CYTOKINES, IL-1 AND IL-6, AND BETA-AMYLOID PRODUCTION IN CULTURES

To investigate the role of IL-6 in the pathogenesis of Alzheimer's dis ease (AD) its effect on amyloid precursor protein (APP) mRNA expressio n was evaluated. The levels of APP mRNA were determined by Northern bl ot analysis in primary cultured rat cortical neurons and glial cells e xposed to IL-6 (50-200 ng/ml). The cytokine increased neuronal APP mRN A expression about 100% at the highest dose after 6 h of exposure. APP mRNA expression was unaffected in astroglial cells exposed to IL-6. S ince IL-1 beta also increased neuronal APP mRNA, the combination of IL -1 beta and IL-6 was tested. The effects were partially additive. The ability of beta-amyloid fragment 25-35 to induce IL-1 or IL-6 mRNA was also investigated in astroglial cells. IL-1 beta mRNA was strongly in duced by beta 25-35 (25-100 mu M) while the expression of IL-6 mRNA re maining unchanged. The results suggest roles for both IL-1 and IL-6 in the neuronal mechanisms related to beta-amyloid protein deposition in AD.