BRAIN CYTOKINE MESSENGER-RNAS IN ANORECTIC RATS BEARING PROSTATE ADENOCARCINOMA TUMOR-CELLS

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 a re proposed to be involved in cancer-associated anorexia. Here we inve stigated mRNA profiles of feeding-modulatory cytokines and neuropeptid es in specific brain regions of anorectic Lobund-Wistar rats bearing p rostate adenocarcinoma tumor cells. Interleukin (IL)-1 beta system com ponents (ligand, signaling receptor, receptor accessory proteins, rece ptor antagonist), tumor necrosis factor-alpha, transforming growth fac tor-beta 1, glycoprotein 130 (IL-6 receptor signal transducer), proopi omelanocortin (POMC, opioid peptide precursor), and neuropeptide Y (NP Y) mRNAs were analyzed with sensitive and specific RNase protection as says. The same brain region sample was assayed for all components. The data show that early anorexia in tumor-bearing rats was associated wi th an upregulation of IL-1 beta mRNA in the brain regions examined (ce rebellum, cortex, and hypothalamus). IL-1 receptor antagonist (IL-1Ra) mRNA and IL-1 receptor type I mRNA levels were also significantly inc reased in the cortex and hypothalamus. All other cytokine components, POMC, or NPY mRNA levels were not significantly different between tumo r-bearing and pair-fed (control) rats. IL-1 beta mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen of tumor-bearing rat s. These data suggest that 1) IL-1 beta 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 underl ying molecular mechanisms responsible for cancer-associated neurologic al manifestations.