Table II.

Factors Contributing to Cancer Cachexia in Pediatric Oncology Patients

Sources of energy imbalance	Potential mechanisms
Inflammation causing low energy intake and/or anorexia	Cytokines released by tumor, immune, and stromal cells alter central nervous system transmitters and affect appetite Tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) may increase levels of corticotrophin-releasing peptide, a neurotransmitter that suppresses food intake98 Modulation of gastric motility and emptying Direct effect on gastrointestinal system Alteration of efferent signals regulating satiety; IL-1 blocks feeding stimulated by neuropeptide Y99
Metabolic and endocrine alterations leading to increased catabolic drive	Carbohydrate metabolism Increased fasting insulin levels Increased glucose demand Protein metabolism Loss of normal compensatory protein conservation mechanisms seen in starvation Increased whole-body protein catabolism Increased protein catabolism in muscle cells Decreased regulators of muscle protein synthesis Fat metabolism Accelerated lipolysis driven by inflammatory cytokine inhibition of lipoprotein lipase; TNF-α and Il-6 implicated4 Increased rate of fat oxidation and clearance Decreased lipoprotein-lipase, may shift energy burden to lean body mass Disease burden Metabolic demands of tumor in progressive disease