Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

Figure 1

The growing tumor is sensed by the brain via neural, humoral, and inflammatory input. These signals activate the behavioural and metabolic response to stress by activating microglia cells, although it cannot be excluded that signals from peripheral tissues directly influence the activity of hypothalamic neurons, at least in the initial phase of the response to stress. Microglia activation triggers and perpetuates neuroinflammation, which is characterized by the release of inflammatory mediators within the hypothalamic areas. In the arcuate nucleus, inflammatory response hyperactivates catabolic neurons, that is, melanocortin (MC) neurons, which in turn contribute to the inhibition of prophagic neurons, that is, neuropeptide Y (NPY) neurons. Disruption of the physiological balance between the activity of MC and NPY neurons yields to the behavioural and metabolic consequences of cachexia. Experimental data also suggest that neuroinflammation may contribute to tumour growth and aggressiveness by modulating the peripheral immune response through autonomic output.