RELATIONSHIP BETWEEN INTERLEUKIN-1 AND CANCER ANOREXIA

Interleukin-1 (IL-1) induces anorexia via direct action in the brain, and its participation in the pathogenesis of cancer-associated anorexi a has been hypothesized. Because the functional ablation of the ventro medial nucleus of hypothalamus (VMH), where IL-1 receptors have been d etected, reverses cancer-associated anorexia in tumor-bearing (TB) rat s, we hypothesize that cancer anorexia involves the direct effect of I L-1 on the VMH. To test this hypothesis, we investigated whether the i ntra-VMH injection of the IL-1 receptor antagonist (IL-1(Ra)) improves food intake in anorectic TB rats. Sixteen Fischer rats (similar to 30 0 g/BW) were injected s.c. with 10(6) trypan-blue viable methylcholant hrene sarcoma cells, and then individually caged. Chow and water were freely available, and food intake was recorded throughout the study. N ormal food intake was measured in 8 more rats, injected s.c. with norm al saline. Tumor developed in all rats. When TB rats became anorectic, they were randomly assigned to either treatment or control groups. Us ing stereotaxic techniques, 25 ng of IL-1(ra) dissolved in normal sali ne (TB-IL-1(r)a; n = 8), or an equal volume of normal saline (TB-NS; n = 8) was injected bilaterally into the VMH. After surgery, rats were Caged and changes in food intake recorded. At study's end, rats were s acrificed and brains removed for histological confirmation of injectio n sites. In the TB-NS group, food intake decreased with the occurrence of anorexia. In contrast, the intra-VMH injection of lL-1(r)a, reduce d the severity of cancer anorexia, significantly improving food intake in TB-IL-1(ra) rats. Data indicate that centrally acting IL-1 plays a significant role in the development of cancer anorexia.