Intracerebroventricular interleukin-6, macrophage inflammatory protein-1 beta and IL-18: pyrogenic and PGE(2)-mediated?

This study was undertaken to determine whether cyclooxygenase (COX)-2, the critical enzyme in the production of febrigenic prostaglandin (PG) E(2), may be involved centrally in the fever induced in mice by homologous interleukin (IL)-6, macrophage inflammatory protein (MIP)-1 beta, and interleukin (...

Full description

Saved in:
Bibliographic Details
Published in:Brain research 2003-11, Vol.992 (1), p.76-84
Main Authors: Li, Shuxin, Goorha, Sarita, Ballou, Leslie R, Blatteis, Clark M
Format: Article
Language:English
Subjects:
Animals
Body Temperature - drug effects
Brain - drug effects
Brain - enzymology
Chemokine CCL4
Cyclooxygenase 2
Dose-Response Relationship, Drug
Fever - chemically induced
Fever - enzymology
Injections, Intraperitoneal
Injections, Intraventricular
Interleukin-18 - administration & dosage
Interleukin-18 - pharmacology
Interleukin-6 - administration & dosage
Interleukin-6 - pharmacology
Isoenzymes - physiology
Macrophage Inflammatory Proteins - administration & dosage
Macrophage Inflammatory Proteins - pharmacology
Mice
Prostaglandin-Endoperoxide Synthases - physiology
Recombinant Proteins - administration & dosage
Recombinant Proteins - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study was undertaken to determine whether cyclooxygenase (COX)-2, the critical enzyme in the production of febrigenic prostaglandin (PG) E(2), may be involved centrally in the fever induced in mice by homologous interleukin (IL)-6, macrophage inflammatory protein (MIP)-1 beta, and interleukin (IL)-18, a member of the pyrogenic IL-1 beta family. To this end, the core temperatures (Tc) of COX-1 and COX-2 gene-ablated mice and of their normal wild-type (WT) counterparts were recorded after intracerebroventricular (i.c.v.) challenge with recombinant murine (rm) IL-6 (10 ng/mouse), rmMIP-1 beta (20 pg/mouse), rmIL-18 (0.01-1 microgram/mouse), rmIL-1 beta (positive control; 0.1 microgram/mouse), or their vehicle (0.1% bovine serum albumin [BSA] in sterile phosphate-buffered saline [PBS]; 5 microl/mouse). rmIL-6 caused a approximately 1 degrees C T(c) rise in WT mice that peaked at approximately 120 min and gradually recovered over the next 3 h; COX-1(-/-) mice exhibited a relatively faster (peak at 45 min) and shorter (recovery at 150 min) febrile course, whereas COX-2(-/-) mice did not develop fever. rmMIP-1 beta induced a 1 degrees C fever (peak at 60 min) with a long time course (recovery incomplete at 300 min) in both WT and COX-2(-/-) mice; COX-1(-/-) mice displayed a quick-onset (peak at 40 min) and shorter (recovery at approximately 240 min) fever. rmIL-18 did not cause any thermal response at any dose whether administered intraperitoneally (i.p.) or i.c.v. in WT mice; COX gene-ablated mice, therefore, were not tested. These data indicate that COX-2-dependent PGE(2) is critical for the febrile response to IL-6, but not to MIP-1 beta. IL-18 i.p. or i.c.v. is not pyrogenic.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2003.08.033