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Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark, Delaware 19716-2590
Cancer is
consistently associated with anorexia. The Lobund-Wistar rat model of
prostate cancer exhibits clinical manifestations (including anorexia)
that resemble many aspects of the human disease. Cytokines are proposed
to be involved in cancer-associated anorexia. Here we investigated mRNA
profiles of feeding-modulatory cytokines and neuropeptides in specific
brain regions of anorectic Lobund-Wistar rats bearing prostate
adenocarcinoma tumor cells. Interleukin (IL)-1
system components
(ligand, signaling receptor, receptor accessory proteins, receptor
antagonist), tumor necrosis factor-
, transforming growth
factor-1, glycoprotein 130 (IL-6 receptor signal transducer),
proopiomelanocortin (POMC, opioid peptide precursor), and neuropeptide
Y (NPY) mRNAs were analyzed with sensitive and specific RNase
protection assays. The same brain region sample was assayed for all
components. The data show that early anorexia in tumor-bearing rats was
associated with an upregulation of IL-1 mRNA in the brain regions
examined (cerebellum, cortex, and hypothalamus). IL-1 receptor
antagonist (IL-1Ra) mRNA and IL-1 receptor type I mRNA levels were also
significantly increased in the cortex and hypothalamus. All other
cytokine components, POMC, or NPY mRNA levels were not significantly
different between tumor-bearing and pair-fed (control) rats. IL-1
mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen
of tumor-bearing rats. These data suggest that
1) IL-1 mRNA upregulation in the brain may be relevant to the anorexia exhibited by the tumor-bearing Lobund-Wistar rat and 2) in vivo
characterization of cytokine components in discrete brain regions
during cancer is necessary to understand underlying molecular
mechanisms responsible for cancer-associated neurological
manifestations.
interleukin; tumor necrosis factor; growth factor; nervous system; neuroimmunology; hypothalamus; cortex; cerebellum; cancer; food intake; feeding; anorexia
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