Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli

J Comp Neurol. 2004 Apr 19;472(1):113-29. doi: 10.1002/cne.20052.


Interleukin-1 beta (IL-1 beta) is thought to act on the brain to induce fever, neuroendocrine activation, and behavioral changes during disease through induction of prostaglandins at the blood-brain barrier (BBB). However, despite the fact that IL-1 beta induces the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in brain vascular cells, no study has established the presence of IL-1 receptor type 1 (IL-1R1) protein in these cells. Furthermore, although COX inhibitors attenuate expression of the activation marker c-Fos in the preoptic and paraventricular hypothalamus after administration of IL-1 beta or bacterial lipopolysaccharide (LPS), they do not alter c-Fos induction in other structures known to express prostaglandin receptors. The present study thus sought to establish whether IL-1R1 protein is present and functional in the rat cerebral vasculature. In addition, the distribution of IL-1R1 protein was compared to IL-1 beta- and LPS-induced COX-2 expression. IL-1R1-immunoreactive perivascular cells were mostly found in choroid plexus and meninges. IL-1R1-immunoreactive vessels were seen throughout the brain, but concentrated in the preoptic area, subfornical organ, supraoptic hypothalamus, and to a lesser extent in the paraventricular hypothalamus, cortex, nucleus of the solitary tract, and ventrolateral medulla. Vascular IL-1R1-ir was associated with an endothelial cell marker, not found in arterioles, and corresponded to the induction patterns of phosphorylated c-Jun and inhibitory-factor kappa B mRNA upon IL-1 beta stimulation, and colocalized with peripheral IL-1 beta- or LPS-induced COX-2 expression. These observations indicate that functional IL-1R1s are expressed in endothelial cells of brain venules and suggest that vascular IL-1R1 distribution is an important factor determining BBB prostaglandin-dependent activation of brain structures during infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / immunology
  • Brain / pathology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation, Enzymologic / immunology
  • Humans
  • Inflammation / metabolism
  • Interleukin-1 / metabolism*
  • Interleukin-1 / toxicity
  • Male
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / analysis
  • Receptors, Interleukin-1 / biosynthesis*
  • Receptors, Interleukin-1 Type I


  • Interleukin-1
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • Prostaglandin-Endoperoxide Synthases