Interleukin-1 Receptor-Expressing Cells In The Arcuate Hypothalamus Mediate Reduced Food Intake After Peripheral Administration Of Interleukin-1

Sickness behavior includes low locomotor activity and reduced food intake and is observed during infectious and inflammatory disease. It can be mimicked by peripheral administration of the pro-inflammatory cytokine interleukin-1 (IL1) and are mediated by IL1 action in the brain, that is, behind the IL1 receptors expressed by brain endothelial cells. The present work was undertaken to identify the phenotypes of brain parenchymal IL1 receptor-expressing cells and to determine their role in sickness behavior. Double labeling in situ hybridization was used to identify rat brain parenchymal IL1 receptor-expressing cells. A molecular tool consisting of IL1 coupled to the toxin saporin (IL1-SAP) was used to specifically eliminate IL1 receptor-bearing cells in targeted brain structures and to test their roles in IL1-induced sickness behavior. IL1 type 1 receptor mRNA was expressed by neuropeptide Y neurons in the arcuate hypothalamus and by preprodynorphin mRNA-positive neurons in the basolateral amygdala. Local injection of IL1-SAP into the arcuate hypothalamus specifically reduced the number of neuropeptide Y-expressing neurons and attenuated IL1-induced hypophagia. These findings indicate that IL1 receptor-bearing neuropeptide Y neurons of the arcuate hypothalamus mediate, at least in part, the reduction in food intake after peripheral administration of IL1.