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 pro-inflammatory 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-alpha, 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-alpha 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.