Cytokine and cyclooxygenase-2 protein in brain areas of tumor-bearing micewith prostanoid-related anorexia

Evidence suggests that cytokines in the central nervous system are mediator s behind anorexia in tumor-bearing hosts. We have therefore evaluated, by i mmunohistochemical image analyses, time course changes of interleukin (IL)- 1 beta, IL-6, tumor necrosis factor (TNF) alpha, IL-6 receptor (gp130), IL- 1 receptor I, and cyclooxygenase (Cox)-2 protein in brain cortex, hippocamp us and the ventromedial hypothalamic nucleus (VMH) in tumor-bearing mice wi th prostanoid-related anorexia, Pair-fed nontumor-bearing mice were used as controls. Prostaglandin E, was provided systemically to freely fed, non-tu mor-bearing mice to confirm a role for prostanoids in modulation of brain c ytokines and food intake. Time course changes of IL-1 beta 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 differenc e between tumor-bearing mice and pair-fed controls, whereas TNF-alpha showe d a small increase over time in brain VMH, IL-6 content did not show any si gnificant alterations among tumor-bearing and pair-fed mice but increased s ignificantly over time in both the study and control group. Cox-2 in brain hippocampus and VMH showed a statistically significant rise in both tumor-b earing and pair-fed controls, with no difference between animal groups. Sys temic 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-1 beta) occurred in brain cytokines comparing tumor-bearing and pair-fed, non-tumor -bearing mice but within unexpected decreased levels in brain tissue from t umor-bearing mice, Surprisingly, many time course changes in brain cytokine s were similarly altered in tumor-bearing and pair-fed mice. Our observatio ns do not support that up-regulation of brain cytokines explains or promote s anorexia in cancer disease. Rather, cytokine and Cox-dependent alteration s in brain tissue seemed to be secondary to a decline in food intake and re lated to subsequent stress hormone activities.