The Role of Tumor Necrosis Factor Alpha and TNF Superfamily Members in Bone Damage in Patients with End-Stage Chronic Obstructive Lung Disease Prior to Lung Transplantation

Abstract

A disequilibrium of tumor necrosis superfamily (TNF) members, including the serum osteoprotegerin, soluble receptor activator of nuclear factor-κB ligand, soluble TNF-related apoptosis-inducing ligand and TNF-α, was associated with the occurrence of a reduced skeletal mass and osteoporosis in male patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study was to explore the associations between serum biomarkers of tumor necrosis factor (TNF) superfamily and body and bone compositions in end-stage COPD males. Pulmonary function, T-score at the lumbar spine and femoral neck, lean mass, serum osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL), TNF-α and its receptors (sTNFR-I, sTNFR-II) and soluble TNF-related apoptosis-inducing ligand (sTRAIL) levels were evaluated in 48 male patients with end-stage COPD and 36 healthy male volunteers. OPG was lower in male COPD patients than in control subjects, whereas sRANKL, TNF-α and its receptors were higher. The serum sTRAIL level showed a tendency to increase compared with that of healthy subjects (P = 0.062). Serum OPG showed a positive correlation with bone density. In contrast, serum TNF-α, sRANKL and sTRAIL were inversely associated with pretransplant bone density. We have noted the appearance of statistically significant inverse relationships between lean mass values and TNF-α, sTNFR-I and II and sRANKL levels in male COPD patients. Moreover, there was a negative correlation between sTRAIL levels with airway obstruction (P = 0.005) and hypercapnia (P = 0.042) in advanced COPD patients. Through a multiple linear regression analysis, our study revealed that a disequilibrium of TNF family members was strongly associated with the occurrence of a reduced skeletal mass and osteoporosis. These results provide further evidence that abnormal levels of TNF superfamily molecules may cause not only a decrease in BMD, but also lower muscle mass in end-stage COPD.

Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting

“…Classically, circulating TNF-α is reported to be higher in COPD patients than controls and negatively correlated to lean mass [ 23 , 24 ], as well as to muscle strength, including upper muscles [ 25 ]. However, this correlation seems to be consistent only in cachectic patients [ 26 ].…”

Therapeutic effects of thymoquinone in doxorubicin‐induced hepatotoxicity via oxidative stress, inflammation and apoptosis

“…Excessive formation of reactive oxygen species (ROS), the enervation of the antioxidant defence system and lipid peroxidation of bio-membranes may cause the upregulation of inflammatory pathways and excessive releasing of pro-and anti-inflammatory cytokines such as tumour necrosis factor-alpha (TNFα) and transforming growth factor-beta (TGFβ). Finally, disequilibrium between these cytokines may induce necrosis and apoptosis (Kochetkova et al, 2016).…”

Inflammatory Cytokine Elaboration Following Secondhand Smoke (SHS) Exposure Is Mediated in Part by RAGE Signaling

“…It is mainly secreted by macrophages and damaged epithelial cells; inflammatory pathways are specifically modulated when in their secreted form. We discovered the differential expression of both TNF-α as well as its two main soluble receptor types (sTNFRI and sTNFRII), which dephosphorylate the membrane form of TNF when engaged [50,51].…”