Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome.
In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown.
Systemic IL-6 overexpression in precachectic tumor-bearing Apc<sup>Min/+</sup> mice accelerated cachexia development, which coincided with suppressed basal and eccentric contraction-induced muscle protein synthesis.
Based on these findings, we conclude that chronic inflammation (especially that mediated by IL-6) might promote cancer cachexia by regulating WAT lipolysis in early-stage cachexia and browning in late-stage cachexia.
The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients.
Collectively, these preclinical findings identify trans-signalling via STAT3 as the signalling modality by which IL-6 promotes muscle wasting in lung cancer cachexia, and therefore support the clinical evaluation of the IL-6 trans-signalling/STAT3 axis as a therapeutic target in advanced lung cancer patients presenting with cachexia.
This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes.
In lung cancer patients, were cachexia is prevalent, there was a significant correlation between elevated IL-6 expression in the tumor and poor prognosis of the patients.
Overall, these results demonstrate short-term PDTC treatment to cachectic mice attenuated cancer-induced disruptions to muscle and liver signaling, and these changes were independent to altered tumor burden and circulating IL-6.
The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed.
Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study.
A marked increase (5-fold) in IL-6 as a result of the interaction between the presence of cachexia and the presence of tumour was observed in the subcutaneous tissue of the patients, yet not in the visceral depot.
Interestingly, signs of morbidity (cachexia) in mice treated with MV were not directly associated with tumour burden, but were correlated with the secretion of interleukin-6 by MET-1 cells and host cells.
However, since release of IL-6 is frequent in HCC, especially in its more advanced stages, the use of agents like curcumin or DHMEQ might be beneficial to counteract its adverse systemic effects (e.g., cachexia).
Moreover, IL-6 is a pathophysiological factor in several hyperproliferative diseases and the paraneoplastic syndromes that often accompany cancer, such as cachexia and osteoporosis; thus, anti-IL-6 therapy would be useful in treating these entities as well.