We conclude that anorexia triggers increased reactive microglial density and expression of TNF-α, IL-6 and IL-1β; this environment may result in hippocampal neuroinflammation.
We previously reported that hypothalamic tumor necrosis factor-alpha (TNF-α) mRNA expression via histamine H<sub>4</sub> receptors contributes to the development of cisplatin-induced anorexia; however, its precise mechanisms remain unclear.
TonEBP (+/-) mice show reduced sickness responses, which include anorexia and hyperthermia, that are initially induced by tumor necrosis factor (TNF)-α. TonEBP (+/-) mice also show lower levels of TNF-α-induced hypothalamic expression of POMC and pro-inflammatory cytokines.
In mammals, anorexia accompanying infection is thought to be mediated via cytokines including interleukins, interferons (IFNs), and tumor necrosis factor (TNF).
Cisplatin significantly increased TNF-α mRNA expression in the hypothalamus and spleen, and the period of expression increase paralleled the onset period of anorexia.
Only tumor necrosis factor alphars800629 was associated with anorexia (odds ratio: 0.46; 95% confidence interval: 0.29, 0.72; p < 0.001); patients who were heterozygous and minor homozygous were less likely to suffer anorexia.
During CXRT, controlled for age, sex, race, body mass index, cancer recurrence, previous treatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; p<.05) and to a larger radiation dose to normal lung volume (estimate, 1.77; SE, 0.71; p<.01); an increase in serum IL-6 was significantly related to increased mean severity for the five most severe symptoms (pain, fatigue, disturbed sleep, lack of appetite, sore throat) (estimate, 0.32; SE, 0.16; p<.05).
Current understanding of the pathophysiology of cachexia attributes much of the anorexia and weight loss to the effects of the cytokine tumor necrosis factor (TNF), which is secreted by endotoxin-stimulated macrophages.