title: Cytokine and cyclooxygenase-2 protein in brain areas of tumor-bearing mice with prostanoid-related anorexia.
abstract: Evidence suggests that cytokines in the central nervous system are mediators behind anorexia in tumor-bearing hosts. We have therefore evaluated, by immunohistochemical image analyses, time course changes of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF) alpha, IL-6 receptor (gp130), IL-1 receptor I, and cyclooxygenase (Cox)-2 protein in brain cortex, hippocampus and the ventromedial hypothalamic nucleus (VMH) in tumor-bearing mice with prostanoid-related anorexia. Pair-fed non-tumor-bearing mice were used as controls. Prostaglandin E(2) was provided systemically to freely fed, non-tumor-bearing mice to confirm a role for prostanoids in modulation of brain cytokines and food intake. Time course changes of IL-1beta were significantly different between tumor-bearing mice and pair-fed controls in the hippocampus but not in the VMH. TNF-alpha in the hippocampus and VMH did not show any significant difference between tumor-bearing mice and pair-fed controls, whereas TNF-alpha showed a small increase over time in brain VMH. IL-6 content did not show any significant alterations among tumor-bearing and pair-fed mice but increased significantly over time in both the study and control group. Cox-2 in brain hippocampus and VMH showed a statistically significant rise in both tumor-bearing and pair-fed controls, with no difference between animal groups. Systemic provision of exogenous PGE(2) to non-tumor-bearing mice altered brain cytokines significantly in the hippocampus and VMH with associated changes in food intake. Our results demonstrate that some differences (IL-1beta) occurred in brain cytokines comparing tumor-bearing and pair-fed, non-tumor-bearing mice but within unexpected decreased levels in brain tissue from tumor-bearing mice. Surprisingly, many time course changes in brain cytokines were similarly altered in tumor-bearing and pair-fed mice. Our observations do not support that up-regulation of brain cytokines explains or promotes anorexia in cancer disease. Rather, cytokine and Cox-dependent alterations in brain tissue seemed to be secondary to a decline in food intake and related to subsequent stress hormone activities.
authors.affiliation: Surgical Metabolic Research Laboratory, Lundberg Laboratory for Cancer Research, Department of Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Lönnroth
authors.forename: E
authors.initials: E
authors.lastname: Svanberg
authors.forename: K
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology / Q000378:metabolism*; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C113250:interleukin-6 receptor alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone