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.

Keywords

• Anorexia
• Arcuate hypothalamus
• c-Fos
• corticosterone
• Cyclooxygenase-2
• Extracellular signal-regulated kinase