Peripheral effects of centrally administered interleukin-1beta in mice in relation to its clearance from the brain into the blood and tissue distribution.
Administration of interleukin IL-1 induces acute-phase response and inhibition of gastric secretion more efficiently when administered intracerebroventricularly (i.c.v.) than when the same dose of IL-1 is administered systemically. In this study we describe the pharmacokinetics of IL-1beta, administered centrally or systemically, in the serum or in peripheral tissues. IL-1beta administered i.c.v. resulted in higher peak IL-1beta concentrations, and lasted longer, than intravenous (i.v.) or intraperitoneal (i.p.) administration. Higher IL-1beta levels in the liver and heart were observed after i. c.v. administration (compared to the i.p. or i.v. route). Our data suggest that centrally injected IL-1 induces higher circulating and hepatic IL-1 levels and contributes to the fact that the i.c.v. route of administration is particularly effective in inducing a liver acute-phase response.
Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy.
E
E
Di Santo
F
F
Benigni
D
D
Agnello
J D
JD
Sipe
P
P
Ghezzi
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000493:pharmacokinetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008815:Mice, Inbred Strains; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014018:Tissue Distribution
D000209:Acute-Phase Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D000685:Serum Amyloid A Protein