Brain cyclooxygenase-2 mediates interleukin-1-induced cellular activation in preoptic and arcuate hypothalamus, but not sickness symptoms.
Neurobiology of Disease. 2010-09-01; 39(3): 393-401
Read on PubMed
1. Neurobiol Dis. 2010 Sep;39(3):393-401. doi: 10.1016/j.nbd.2010.05.005. Epub 2010
Brain cyclooxygenase-2 mediates interleukin-1-induced cellular activation in
preoptic and arcuate hypothalamus, but not sickness symptoms.
Nadjar A(1), Sauvant J, Combe C, Parnet P, Konsman JP.
(1)CNRS UMR 5226-INRA 1286, PsychoNeuroImmunologie, Nutrition et Génétique,
Université de Bordeaux, Bordeaux, France.
Interleukin-1beta acts on the CNS to induce fever, neuroendocrine activation, and
behavioral changes, but cannot passively cross the blood-brain barrier. According
to a widely accepted hypothesis interleukin-1beta induces the synthesis of
cyclooxygenase-2 at the blood-brain interface, which produces prostaglandins that
diffuse into brain parenchyma to activate neurons. We studied the role of brain
cyclooxygenase-2 in interleukin-1beta-induced fever, neuroendocrine and
behavioral responses and cellular activation by intracerebroventricular infusion
of the cyclooxygenase-2 inhibitor NS-398. Central cyclooxygenase-2 inhibition
attenuated extracellular signal-regulated kinase-1/2 phosphorylation and c-Fos
induction in the median preoptic area and arcuate hypothalamus, but not in other
hypothalamic or brainstem structures, after intraperitoneal interleukin-1beta
administration. However, the same treatment did not affect
interleukin-1beta-induced fever, rises in corticosterone or anorexia. These
findings moderate the prevailing view and indicate that brain
cyclooxygenase-2-dependent prostaglandin production is important to activation of
the median preoptic and arcuate hypothalamus, but not necessarily involved in
fever, rises in plasma corticosterone and anorexia after peripheral
PMID: 20470889 [Indexed for MEDLINE]