Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells.

Abstract

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)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), tumor necrosis factor-alpha, transforming growth factor-beta1, 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-1beta 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-1beta mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen of tumor-bearing rats. These data suggest that 1) IL-1beta 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.