Brain cyclooxygenase-2 mediates interleukin-1-induced cellular activation in preoptic and arcuate hypothalamus, but not sickness symptoms.
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 interleukin-1beta administration.
Nadjar
Agnès
A
CNRS UMR 5226-INRA 1286, PsychoNeuroImmunologie, Nutrition et Génétique, Université de Bordeaux, Bordeaux, France.
Sauvant
Julie
J
Combe
Chantal
C
Parnet
Patricia
P
Konsman
Jan Pieter
JP
D000704:Analysis of Variance; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D055809:Illness Behavior / Q000187:drug effects*; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; D009578:Nitrobenzenes; D016760:Proto-Oncogene Proteins c-fos; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003345:Corticosterone