The present application proposes to explore the role of proinflammatory cytokines in the brain. The investigators contend that although a great deal of knowledge regarding the role of proinflammatory cytokines in cachexia exists, there has been little investigation into systemic effects of CNS produced or administered cytokine. The investigator's working hypothesis is that a major component of the wasting of AIDS is caused directly by cytokines produced within the CNS. The studies proposed contain three objectives: 1) to compare the wasting properties of the three proinflammatory cytokines (TNF alpha, IL-1 beta and IL-6) injected into the lateral ventricle of the brain; 2) to identify and localize the receptors for TNF, IL-1 and IL-6 in the brain responsible for the cachexia; and 3) to employ novel approaches to block cytokine induced wasting by administering to the CNS cytokine antagonists. In this manner, the investigators state that they will address critically important, but as yet relatively unexplored area in the pathogenesis of wasting by carefully defining the role of cytokines and their receptors in the CNS.
Showing the most recent 10 out of 38 publications
