Brain cytokine mRNAs 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 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.
Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark, Delaware 19716-2590, USA.
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Plata-Salamán
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Ilyin
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Gayle
D000230:Adenocarcinoma / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011471:Prostatic Neoplasms / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009478:Neuropeptide Y; D009479:Neuropeptides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D011333:Pro-Opiomelanocortin