IL-6 family cytokines in respiratory health and disease

Proposed novel treatment paradigm of aberrant gait and balance kinematics in patients with severe COPD

“…4,5,[11][12][13][14] Moreover, home confinement imposed by limited mobility of these patients may amplify systemic inflammation through the F I G U R E 1 Effects of aberrant gait and balance kinematics on severe COPD outcomes deleterious effects of inadequate household air quality on cardiopulmonary function. 15 Support for our hypothesis comes from the study of Brinkley et al 13 who found that increased circulating concentrations of IL-6, a potent, pleiotropic pro-inflammatory cytokine elaborated and released by a plethora of stromal and migrant cells in response to various noxious stimuli, including oxidative stress, 16,17 but not of TNF-α, were associated with poorer physical function, including longer times to complete the 4-min walk and repeated chair stands tests, in a large cohort of older patients with COPD enrolled in four clinical studies at Wake Forest University in North Carolina, USA. In addition, Verghese et al 14 showed that patients with COPD have high circulating IL-6 concentrations in comparison to controls.…”

“…The mechanistic basis underlying elaboration and release of IL‐6 in the lung and extra‐pulmonary organs of patients with severe COPD has not been delineated. To that end, ventilatory muscle overactivation during loaded breathing in these patients could generate reactive oxygen species which, in turn, elicit a cascade of systemic inflammatory response involving generation of potent pro‐inflammatory cytokines, including IL‐6 4,5,11,16 . This hypothesis is supported, in part, by the study of Savelikhina et al 18 who showed that treatment with roflumilast, a US FDA‐approved long‐acting inhibitor of the enzyme phosphodiesterase‐4 with antioxidant properties, 19,20 for 180 days reduced IL‐6 concentrations in bronchoalveolar lavage fluid of 61 patients with severe COPD.…”

“…Higher IL‐6 concentrations, but not of TNF‐α, were associated with slower gait velocity and faster gait speed decline over time in older adults. Finally, high circulating IL‐6 concentrations may also adversely affect brain function leading to cognitive impairment 16 …”

“…Finally, high circulating IL-6 concentrations may also adversely affect brain function leading to cognitive impairment. 16 The mechanistic basis underlying elaboration and release of IL-6 in the lung and extra-pulmonary organs of patients with severe COPD has not been delineated. To that end, ventilatory muscle overactivation during loaded breathing in these patients could generate reactive oxygen species which, in turn, elicit a cascade of systemic inflammatory response involving generation of potent pro-inflammatory cytokines, including IL-6.…”

SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis

“…59 On top of predominantly greater neutrophil to lymphocyte ratios in severe cases of COVID-19, 60 hyperinflammation and highly elevated concentrations of cytokines and chemokines drive the severity of disease, 61 of which macrophages constitute a significant source. 59,62 IL-6 and the NF-κB pathway is heavily implicated and highly correlated with lethal complications from COVID-19, 56,63 and given the role of IL-6 in chronic respiratory diseases, 64,65 smoking and COPD could initiate and exacerbate the severity of COVID-19 cytokine storm. 62 It has recently been suggested that the smoking-induced increase in ACE2 expression is nicotine-dependent and mediated by α7-subtype nicotinic receptors (α7-nAChR).…”