Site-specific modulation of LPS-induced fever and interleukin-1 beta expression in rats by interleukin-10.
Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic cytokines such as interleukin (IL)-1 beta. We hypothesized that the anti-inflammatory cytokine IL-10 modulates the febrile response to LPS by suppressing the production of pyrogenic cytokines. In rats, intravenous but not intracerebroventricular infusion of IL-10 was found to attenuate fever induced by peripheral administration of LPS (10 microg/kg iv). IL-10 also suppressed LPS-induced IL-1 beta production in peripheral tissues and in the brain stem. In contrast, central administration of IL-10 attenuated the febrile response to central LPS (60 ng/rat icv) and decreased IL-1 beta production in the hypothalamus and brain stem but not in peripheral tissues and plasma. Furthermore, intravenous LPS upregulated expression of IL-10 receptor (IL-10R1) mRNA in the liver, whereas intracerebroventricular LPS enhanced IL-10R1 mRNA in the hypothalamus. We conclude that IL-10 modulates the febrile response by acting in the periphery or in the brain dependent on the primary site of inflammation and that its mechanism of action most likely involves inhibition of local IL-1 beta production.
Ledeboer
Annemarie
A
Research Institute Neurosciences Free University, Department of Medical Pharmacology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
Binnekade
Rob
R
Brevé
John J P
JJ
Bol
John G J M
JG
Tilders
Fred J H
FJ
Van Dam
Anne-Marie
AM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000378:metabolism*; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053701:Receptors, Interleukin-10; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10