The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI.
The excessive levels of tumor necrosis factor-alpha (TNF)/cachectin reported in 50% of cancer patients exhibiting clinically active disease may therefore mediate, at least in part, the cachexia associated with malignancy.
The syndrome of cachexia associated with malignant diseases can be in part attributed to the effects of tumour necrosis factor alpha (TNFalpha) which itself is produced by a variety of tumour cells.
In this study, weight loss, body mass index, skeletal muscle index (SMI), serum carcinoembryonic antigen, serum tumor necrosis factor (TNF)-α, serum interleukin (IL)-6, serum high mobility group box (HMGB)-1, and SDS-soluble myosin light chain 1 (SDS-MYL1) of the psoas muscle were examined in 8 autopsied cases of death from colorectal cancer (CRC) as biomarkers of cachexia.
Inducible nitric oxide synthase (iNOS) has recently been shown to be an important mediator of TNFα-induced cachectic muscle loss, and studies suggest that it may also play a role in sarcopenia.
In addition, TNF-alpha mice displayed impaired healing of incisional and excisional skin wounds, compared with control animals, before the onset of cachexia.
These results suggest that the evaluation of TNF/cachectin and LT production in lymphomas may help to elucidate the mechanisms of tumoral fever and cachexia.
We investigated AT expressions of interleukin (IL)-6, tumor necrosis factor (TNF)-α, CD68 (macrophage cell surface receptor), caspase-3, and Bax, and their relationships to the metabolic phenotype in nine cachectic, 12 normal-weight, 12 overweight, and 11 obese patients with COPD (age 62.3 ± 7.2 years).
A number of pro-inflammatory cytokines, like interleukin-1 (IL-1), IL-6, tumor necrosis factor- alpha (TNF-α) may have important role in the pathological mechanisms of cachexia in cancer.
However, from various studies it has become clear that the action of TNF can only be understood in the context of simultaneous presence of other cytokines, some of which have activities that are at the least equally important as TNF in bringing about cachexia.
The basis for these interactions between TNF and IGF-1 is discussed with specific reference to clinical consequences for myofibre necrosis in DMD and also for the wasting (atrophy) of skeletal muscles that occurs in very old people and in cachexia associated with inflammatory disorders.
It has further been suggested that TNF may play a role in the pathobiochemistry of CF cachexia, secondary to the localized inflammatory response in the lung or wider systemic activation of cells of the monocyte-macrophage series in response to endotoxin.
Expression of a constitutively active mutant of Gα(i2) stimulated myotube growth and differentiation, effects that required the transcription factor NFAT (nuclear factor of activated T cells) and protein kinase C. In addition, expression of the constitutively active Gα(i2) mutant inhibited atrophy caused by the cachectic cytokine TNFα (tumor necrosis factor-α) by blocking an increase in the abundance of the mRNA encoding the E3 ubiquitin ligase MuRF1 (muscle ring finger 1).
Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome.