Cachexia or disease-associated wasting is a significant problem in the treatment of many chronic diseases. Prior research has implicated the central melanocortin system as playing an important role in this process seen in that introduction of melanocortin antagonists attenuates cachexic responses to inflammation. Our lab has shown that pro-opiomelanocortin- (POMC-) producing neurons in the arcuate nucleus of the hypothalamus are activated during inflammation and that approximately 35% of arcuate POMC neurons express cytokine receptors. The brainstem is also a site of POMC expression and because the brainstem is involved in producing many of the physiologic processes observed in cachexia, we have been investigating the response of POMC-expressing neurons in the brainstem following introduction of IL-1. We have found a significant increase in the amount of POMC cells with c-fos activation and electrical activity following IL-1 exposure. We propose to study whether this effect is produced via direct or indirect activation and whether other cytokines produce a similar activation in POMC neurons in the brainstem. We further propose to study the physiologic response seen when brainstem melanocortin activity is blocked via pharmicologic means. ? ? ?
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