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 processseen in that introduction of melanocortin antagonists attenuates cachexic responses to inflammation. Ourlab has shown that pro-opiomelanocortin- (POMC-) producing neurons in the arcuate nucleus of thehypothalamus are activated during inflammation and that approximately 35% of arcuate POMC neuronsexpress cytokine receptors. The brainstem is also a site of POMC expression and because the brainstem isinvolved in producing many of the physiologic processes observed in cachexia, we have been investigatingthe response of POMC-expressing neurons in the brainstem following introduction of IL-1. We have found asignificant increase in the amount of POMC cells with c-fos activation and electrical activity following IL-1exposure. We propose to study whether this effect is produced via direct or indirect activation and whetherother cytokines produce a similar activation in POMC neurons in the brainstem. We further propose to studythe physiologic response seen when brainstem melanocortin activity is blocked via pharmicologic means.
