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Brain cyclooxygenase-2 mediates interleukin-1-induced cellular activation in preoptic and arcuate hypothalamus, but not sickness symptoms

Abstract : Interleukin-1ß 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-1ß 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-1ß-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-1ß administration. However, the same treatment did not affect interleukin-1ß-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-1ß administration.
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Submitted on : Sunday, May 31, 2020 - 12:14:27 PM
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Agnès Nadjar, Julie Sauvant, Chantal Combe, Patricia Parnet, Jan Peter Konsman. Brain cyclooxygenase-2 mediates interleukin-1-induced cellular activation in preoptic and arcuate hypothalamus, but not sickness symptoms. Neurobiology of Disease, Elsevier, 2010, 39 (3), pp.393-401. ⟨10.1016/j.nbd.2010.05.005⟩. ⟨hal-02668167⟩

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