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Characterization of IL-6 and GDF15 expression during the transition from pre-anorexia to anorexia in the C26 tumor-bearing mouse model
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International audience. Introduction: Anorexia is a major symptom of cachexia for a large number of cancer patients, disrupting the physiological regulation of food intake and contributing to the deterioration of health status. Data from literature suggest that mechanisms underlying cancer-associated anorexia may involve both central and peripheral mediators, such as IL-6 and GDF15 cytokines, but they are poorly understood. Our objective was to study the mechanisms associated to the transition from pre-anorexia to anorexia. Methods: We chose the C26 tumor-bearing mouse model characterized by a decreased food intake and loss of body weight (Bindels et al., Oncotarget 2018). The food intake of C26- and Sham male mice was measured daily. We performed biological analyses on two groups of C26-mice, on pre-anorexia stage and early stage of anorexia. Results: The onset of anorexia was associated with a significant increase in the weight of tumor, spleen and liver. In the hypothalamus, a key site of food intake regulation, the mRNA expression level of IL-6, IL-1β and TNF cytokines were not affected. The expression level of the orexigenic neuropeptide NPY was significantly increased. At the peripheral level, food intake was inversely correlated with plasma levels of IL-6 and GDF15 cytokines (R2=0.82 and 0.70, respectively). Plasma GDF15 concentrations correlated with tumor mass (R2=0.57), but the expression level of GDF15 mRNA did not change over time in the tumor, whereas it was increased in liver and intestine. Conversely, the expression level of IL-6 mRNA was high and increased over time within the tumor whereas it was not detectable in liver and intestine. Conclusions: The magnitude of anorexia is correlated with circulating levels of IL-6 and GDF15, underlying the potential involvement of these cytokines. However, IL-6 and GDF15 expressions are regulated in different ways among the different tissues.
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