Interleukin-1 receptors on rat brain endothelial cells: a role in neuroimmune interaction?
Inflammation following an infection induces a range of nonspecific symptoms of sickness in animals and humans. The cytokine interleukin-1 (IL-1) mediates many of the brain-mediated symptoms of sickness. Binding sites for IL-1 have been found in mouse brain, but not in the brains of rats. This raises questions as to the involvement of these neuronally localized IL-1 binding sites in the induction of sickness symptoms. Based on observations of IL-1 receptor mRNA in close vicinity to the vasculature in the mouse and rat brain, we studied the possibility that endothelial cells in the rat brain exhibit IL-1 receptors to transduce information to the brain. Ligand binding studies reveal that cultured endothelial cells of adult rat brain exhibit specific binding sites for rat IL-1beta. Polymerase chain reaction experiments demonstrated that mRNA of the type I but not that of the type II IL-1 receptor is present in rat brain endothelial cells. Incubation of these endothelial cells with recombinant rat IL-1beta showed a dose-dependent increase in interleukin-6, prostaglandin E(2), and prostacyclin secretion. Intravenous administration of rat IL-1beta to adult rats enhanced prostaglandin E(2) immunoreactivity in endothelial cells of the brain microvasculature. These results indicate that functional type I IL-1 receptors are present on endothelial cells of adult rat brain. We postulate that circulating IL-1 can be translated by brain endothelial cells into other signals such as interleukin-6 or prostaglandins that have access to the brain and induce sickness symptoms.
Van Dam
A M
AM
Research Institute Neurosciences Free University, Medical Faculty, Amsterdam, The Netherlands.
De Vries
H E
HE
Kuiper
J
J
Zijlstra
F J
FJ
De Boer
A G
AG
Tilders
F J
FJ
Berkenbosch
F
F
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D015232:Dinoprostone