Central β‐amyloid peptide‐induced peripheral interleukin‐6 responses in mice

β‐Amyloid peptides (Aβs) share with lipopolysaccharide, a potent pro‐inflammatory agent, the property of stimulating glial cells or macrophages to induce various inflammatory mediators. We recently reported that central administration of lipopolysaccharide induces peripheral interleukin‐6 responses via both the central and peripheral norepinephrine system. In this study, the effect of intracerebroventricular injection of various synthetic Aβs on plasma interleukin‐6 levels was examined in mice. Aβ 1−42 dose‐dependently increased plasma interleukin‐6 levels: ‘aged’ Aβ 1−42 was more effective than fresh, whereas Aβ 42−1 had no effect. ‘Aged’ Aβ 1−42 (205 pmol/mouse i.c.v.)‐induced plasma interleukin‐6 peaked at 2 h post injection, which is earlier than the peak time of the Aβ 1−42 ‐induced brain interleukin‐6, tumor necrosis factor‐α and interleukin‐1β levels, which was 4, 4 and 24 h, respectively. Among various peripheral organs, Aβ 1−42 (205 pmol/mouse i.c.v.) significantly increased interleukin‐6 mRNA expression in lymph nodes and liver. Aβ 1−42 (205 pmol/mouse i.c.v.) significantly increased norepinephrine turnover in both hypothalamus and spleen. Either central or peripheral norepinephrine depletion effectively inhibited the Aβ 1−42 ‐induced peripheral interleukin‐6 response. Pretreatment with prazosin (α 1 ‐adrenergic antagonist), yohimbine (α 2 ‐adrenergic antagonist), and ICI‐118,551 (β 2 ‐adrenergic antagonist), but not with betaxolol (β 1 ‐adrenergic antagonist), inhibited Aβ 1−42 ‐induced plasma interleukin‐6 levels. These results demonstrate that centrally administered Aβ 1−42 effectively induces the systemic interleukin‐6 response which is mediated, in part, by central Aβ 1−42 ‐induced activation of the central and the peripheral norepinephrine systems.