What Role Do Inflammatory Cytokines Play in Cancer Cachexia?

Abstract

A tumor extends its effects beyond its local site, and one such effect is cancer cachexia which is caused by a state of systemic inflammation in response to cancer. Though the prominent effect of cancer cachexia is seen on skeletal muscles, it shows deterioration in other organs' smooth muscle, adipose tissue, blood, bone marrow, liver, and immunity. Interleukin (IL)-6 plays an imminent role along with tissue necrosis factoralpha, IL-1 beta, interferon-gamma, myostatin, adiponectin, growth differentiation factor-15, activin A, etc. These cytokines through nuclear factor-kappa beta, mitogen-activated protein kinase, suppressor of mothers against decapentaplegic, and Janus activated kinase/signal transducer and activator of transcription pathway activate genes inducing ubiquitin-proteosome system and reactive oxidative species. Apart from these, they participate in causing anemia and immunosuppression. Adipose tissue acts as a source of cytokines and place of action of cytokines leading to lipolysis. Moreover, these cytokines act at the hypothalamic-pituitary-adrenal axis change metabolism and add to anorexia which already exists in cancer patients. The involvement of multiple cytokines necessitates the development and testing of anti-cytokines in combinations.

Drug‐related sarcopenia as a secondary sarcopenia

“…Inflammation is believed to be a major factor in skeletal muscle wasting associated with cachexia. In particular, the response of skeletal muscle itself to various inflammatory cytokines induces muscle atrophy 81 . Interferon (IFN) is a cytokine released from inflammatory cells, and its effects on skeletal muscle include suppression of myoblast differentiation, increased muscle protein catabolism via increased atrogin mRNA expression in myotubes, and induction of mitochondrial dysfunction in muscle tissue 82 .…”

“…In particular, the response of skeletal muscle itself to various inflammatory cytokines induces muscle atrophy. 81 Interferon (IFN) is a cytokine released from inflammatory cells, and its effects on skeletal muscle include suppression of myoblast differentiation, increased muscle protein catabolism via increased atrogin mRNA expression in myotubes, and induction of mitochondrial dysfunction in muscle tissue. 82 In fact, IFN (types I, II, and III) has been implicated in the pathogenesis of idiopathic inflammatory myopathies, and the effects of IFN on skeletal muscle are noteworthy.…”

Role of growth differentiation factor 15 in cancer cachexia (Review)

“…The occurrence of CC has been attributed to systemic inflammation generated by tumor-host interactions and tumor-derived catabolic factors such as proteolysis-inducing factor, zinc-α2-glycoprotein (ZAG), parathyroid hormone-related protein and microRNAs (miRNAs) (6,7). Systemic inflammation is characterized by increased circulating levels of cytokines, including tumor necrosis factor (TNF)-α, TNF-like weak inducer of apoptosis, interleukin (IL)-1, IL-6, IL-8, IL-20, interferon-γ, leukemia inhibitory factor, myostatin, activin and growth differentiation factor 15 (GDF15) (10)(11)(12)(13). These factors drive metabolic disorders in multiple tissues and organs during CC, including the muscles (10,11,13,14), adipose tissue (10)(11)(12)15,16), heart (17), brain (10,11), liver (10,(18)(19)(20)(21), gallbladder (19), bone (22), pancreas (21), spleen (18), intestines (23), gonads (24) and blood (18,22,25).…”

“…Systemic inflammation is characterized by increased circulating levels of cytokines, including tumor necrosis factor (TNF)-α, TNF-like weak inducer of apoptosis, interleukin (IL)-1, IL-6, IL-8, IL-20, interferon-γ, leukemia inhibitory factor, myostatin, activin and growth differentiation factor 15 (GDF15) (10)(11)(12)(13). These factors drive metabolic disorders in multiple tissues and organs during CC, including the muscles (10,11,13,14), adipose tissue (10)(11)(12)15,16), heart (17), brain (10,11), liver (10,(18)(19)(20)(21), gallbladder (19), bone (22), pancreas (21), spleen (18), intestines (23), gonads (24) and blood (18,22,25). Table I summarizes the cytokines involved in the damage of various organs or tissues associated with CC.…”

Anti-nucleolin aptamer, iSN04, inhibits the inflammatory responses in myoblasts by modulating the β-catenin/NF-κB signaling pathway

“…One of the causes of muscle wasting in chronic diseases is systemic inflammation induced by circulating factors such as pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs) [9,10].…”