INTRACEREBROVENTRICULAR INJECTION OF ANTI-FAS ACTIVATES THE HYPOTHALAMUS-PITUITARY-ADRENAL AXIS AND INDUCES PERIPHERAL INTERLEUKIN-6 AND SERUM AMYLOID-A IN MICE - COMPARISON WITH OTHER LIGANDS OF THE TUMOR-NECROSIS-FACTOR NERVE GROWTH-FACTOR RECEPTOR SUPERFAMILY

Fas is a receptor of the tumor necrosis factor (TNF)/nerve growth fact or (NGF) receptor superfamily that mediates apoptosis and some inflamm atory changes. As the central administration of TNF is known to activa te the hypothalamus-pituitary-adrenal axis (HPAA) and to induce periph eral responses including induction of serum interleukin (IL)-6 and ser um amyloid A (SAA), we investigated the effects of intracerebroventric ular (i.c.v.) administration of agonist anti-Fas monoclonal antibody J o2. Centrally administered anti-Fas (1 mu g/mouse, i.c.v,) induced ele vated levels of corticosterone, IL-6, and SAA comparable to those obse rved after i.c.v. administration of recombinant murine TNF. On the oth er hand, administration of murine NGF did not elevate serum corticoste rone or IL-6, but induced SAA. Thus, Fas can trigger a centrally media ted anti-inflammatory response (HPAA activation) and induce a peripher al acute-phase response comparable to that induced with TNF, whereas N GF induces only acute-phase proteins.