Reduced ingestion of sweetened milk induced by interleukin-1 and lipopolysaccharide is associated with induction of cyclooxygenase-2 in brain endothelia.
Previous studies have shown that interleukin-1 (IL-1) and lipopolysaccharide (LPS) administration to animals induces behavioral changes, including a reduction in feeding. These effects of IL-1 and LPS have been shown to be sensitive to inhibitors of cyclooxygenase (COX).


OBJECTIVE
To determine the relationships between induction of COX-2 in the brain with IL-1beta- and LPS-induced changes in body temperature, plasma corticosterone and feeding.


METHODS
Mice were injected with intraperitoneal doses of IL-1beta and LPS that decreased feeding. The induction of COX-2 was studied immunocytochemically in the brain, in parallel with core body temperature, the drinking of sweetened milk, and plasma concentrations of corticosterone.


RESULTS
COX-2 immunoreactivity (ir) was sparse in the brains of the untreated mice, but IL-1beta and LPS both increased its expression. This COX-2 induction appeared to be confined to blood vessels, and was not markedly region specific. Induction was evident 30 min after IL-1 or LPS, and was greater at 90 than at 30 min. COX-2-ir in the parenchyma did not change significantly. Thus induction of COX-2 occurred in brain endothelia in parallel with the reduction in feeding. This is consistent with the previously determined sensitivity of IL-1-induced changes in feeding to selective COX-2 inhibitors, and the responses to IL-1 in COX-2-deficient mice. The time courses of the IL-1- and LPS-induced increases in plasma corticosterone paralleled those in the reduction in milk drinking, however, the changes in body temperature appeared later.


CONCLUSIONS
Endothelial COX-2 may be involved in IL-1- and LPS-induced decreases in milk drinking, and possibly in the HPA axis activation. The decreased milk drinking may occur when IL-1 and LPS bind to receptors on brain endothelial cells subsequently inducing COX-2 and the production of prostanoids which elicit the reductions in milk drinking. Thus the behavioral effects of peripherally administered IL-1 and LPS appear to be mediated by multiple mechanisms, including endothelial COX-2, and vagal afferents.
Dunn
Adrian J
AJ
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA. adunn@lsuhsc.edu
Swiergiel
Artur H
AH
Zhang
Hao
H
Quan
Ning
N
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000276:immunology; D001831:Body Temperature / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000201:enzymology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology* / Q000276:immunology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D001068:Feeding and Eating Disorders / Q000201:enzymology* / Q000276:immunology* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000276:immunology; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008892:Milk / Q000378:metabolism; D012803:Sick Role; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000276:immunology; D017833:Visceral Afferents / Q000187:drug effects / Q000276:immunology
D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D003345:Corticosterone