Reciprocal control of inflammatory cytokines, IL-1 and IL-6, and β-amyloid production in cultures

To investigate the role of IL-6 in the pathogenesis of Alzheimer's disease (AD) its effect on amyloid precursor protein (APP) mRNA expression was evaluated. The levels of APP mRNA were determined by Northern blot analysis in primary cultured rat cortical neurons and glial cells exposed to IL-6 (50-200 ng/ml). The cytokine increased neuronal APP mRNA expression about 100% at the highest dose after 6 h of exposure. APP mRNA expression was unaffected in astroglial cells exposed to IL-6. Since IL-1β also increased neuronal APP mRNA, the combination of IL-1β and IL-6 was tested. The effects were partially additive. The ability of β-amyloid fragment 25-35 to induce IL-1 or IL-6 mRNA was also investigated in astroglial cells. IL-1β mRNA was strongly induced by β25-35 (25-100 μM) while the expression of IL-6 mRNA remaining unchanged. The results suggest roles for both IL-1 and IL-6 in the neuronal mechanisms related to β-amyloid protein deposition in AD.