Pro-inflammatory cytokines and oxidative stress/antioxidant parameters characterize the bio-humoral profile of early cachexia in lung cancer patients

Abstract

Cancer-related cachexia, that is present in about 50% of cancer patients and accounts for 20% of all cancer deaths, is clinically characterized by progressive weight loss, anorexia, metabolic alterations, asthenia, depletion of lipid stores and severe loss of skeletal muscle proteins. The main biochemical and molecular alterations that are responsible for the syndrome are prematurely present in the progress of the disease and the identification of the early stages of cachexia can be useful in targetting patients who will benefit from early treatment. The aim of the present study was to delineate the bio-humoral profile of a group of lung cancer patients either non-cachectic or cachectic by evaluating serum proinflammatory cytokines and oxidative stress/antioxidant parameters (both recognized to be involved in cachexia pathogenesis) and pro-inflammatory cytokine gene expression in PBMC (Peripheral blood mononuclear cells) of cancer patients. All serum pro-inflammatory cytokines and oxidative stress/antioxidant parameters significantly increased in neoplastic patients, but only TNF-α, ROS, GSH and vitamin E showed a significantly greater increase in cachectic patients. Pro-inflammatory cytokine gene expression mirrored serum level behaviour except for IL-6 that was increased in serum but not as gene expression, suggesting its provenience from tumour tissue. Our data support that the simultaneous determination of ROS, GSH, vitamin E, together with TNF-α allows the identification of a lung cancer patient developing cancer-related cachexia. This bio-humoral profile should be used for the early diagnosis and follow-up of the syndrome. Moreover, the evaluation of gene expression in patient PBMC was helpful in differentiating tumour vs host factors, therefore being useful in the study of pathogenetic mechanisms in neoplastic cachectic patients.

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

“…Taken together, these data suggest that oxidative stress might be an important inducer of MIC-1 production. The presence of increased oxidative stress (18)(19)(20) could potentially explain why both cachectic and obese patients display increased MIC-1 levels. We suggest that both extreme cachexia in cancer patients and morbid obesity may result in nutritional stress and subsequently oxidative stress in adipocytes and other tissues which may in turn stimulate MIC-1 production.…”

Cachexia and sarcopenia: mechanisms and potential targets for intervention

“…Alterations in some of the proteins participating in this synergy -such as mitofusin -have been described in experimental cancer cachexia [21]. Cytokines, TNF-a, in particular, are associated with increased oxidative stress in skeletal muscle during cancer [22]. Padrao et al [23], using a bladder cancer rat model of muscle wasting, concluded that mitochondrial dysfunction was associated with an accumulation of oxidized and nitrated proteins not repairable by mitochondrial proteases and the mitochondrial shaping machinery [24 ] (Figure 1).…”

“…Mol Cell Endocrinol 2013, 379: [19][20][21][22][23][24][25][26][27][28][29]. The focus of this review was to discuss promising human physiological systems underpinning the decline of mitochondrial and skeletal muscle health with advancing age while highlighting therapeutic strategies such as aerobic exercise and caloric restriction for combating age-related functional impairments.…”

<smlcap>L</smlcap>-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-&#947; Signaling Pathway

“…The utilization of NEFAs in the liver is attenuated [2], mainly due to decreased expression levels and activities of carnitine palmitoyltransferases I and II (CPT I and CPT II) which accelerate fatty acid β-oxidation [3,4]. Additionally, some pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and interferon-γ (IFN-γ) inhibit the lipoprotein lipase, thus preventing adipocytes from storing fatty acids [5]. …”