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 factor (NGF) receptor superfamily that mediates apoptosis and some inflammatory changes. As the central administration of TNF is known to activate the hypothalamus-pituitary-adrenal axis (HPAA) and to induce peripheral responses including induction of serum interleukin (IL)-6 and serum amyloid A (SAA), we investigated the effects of intracerebroventricular (i.c.v.) administration of agonist anti-Fas monoclonal antibody Jo2. Centrally administered anti-Fas (1 microg/mouse, i.c.v.) induced elevated levels of corticosterone, IL-6, and SAA comparable to those observed after i.c.v. administration of recombinant murine TNF. On the other hand, administration of murine NGF did not elevate serum corticosterone or IL-6, but induced SAA. Thus, Fas can trigger a centrally mediated anti-inflammatory response (HPAA activation) and induce a peripheral acute-phase response comparable to that induced with TNF, whereas NGF induces only acute-phase proteins.
Benigni
F
F
Laboratory of Neuroimmunology, Mario Negri Institute for Pharmacological Research, Milano, Italy.
Sacco
S
S
Aloe
L
L
Ghezzi
P
P
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001053:Apolipoproteins / Q000096:biosynthesis*; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000096:biosynthesis*; D008024:Ligands; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D019014:fas Receptor / Q000276:immunology*
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D015850:Interleukin-6; D008024:Ligands; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D000685:Serum Amyloid A Protein; D019014:fas Receptor; D003345:Corticosterone