The Role of Interleukin-6 Signaling in Development of Systemic Inflammation in Chronic Obstructive Pulmonary Disease

Abstract

The review focuses on the role of interleukin-6 (IL-6) signaling in the development of a systemic inflammatory process in chronic obstructive pulmonary disease (COPD). In most researches the attention is paid to local inflammation in COPD. However, it is known that the pathology is characterized by a systemic inflammatory process, which is manifested in the increased levels of proinflammatory mediators in blood flow, and the study of the molecular mechanisms of its development is very important for the therapy of the disease. One of the key mediators of systemic inflammation is cytokine IL-6 which has pro- and antiinflammatory properties. Its effect on the cells is determined by the type of signaling. Nowadays three types of IL-6 signaling are identified: transsignaling, classical and cluster signaling. The review presents the known pathophysiological mechanisms of the development of systemic inflammation in COPD involving IL-6. As a proinflammatory cytokine, IL-6 performs the following functions: transmission of a signal on lung tissue damage, initiation of leukocyte migration into the inflammation site, inhibition of T-cell apoptosis into the inflammation site, influence on T helper differentiation, participation in pathophysiological reactions of development of emphysema and fibrosis. The significance of IL-6 transsignaling for the development of inflammation in COPD has been confirmed by many studies, while there are practically no works devoted to the study of classical IL-6 signaling in COPD. The data presented in the review indicate the need for further study of the role of different types of IL-6 signaling, especially classical signaling, in the regulation of systemic inflammation in COPD.

Features of cytokine signaling forming T-helper immune response in COPD of varying severity

“…According to modern studies, the implementation of IL-6 properties depends on the type of cell signaling [9]. The IL-6 receptor complex consists of IL-6R subunit, which is responsible for cytokine binding, and gp130 subunit, which provides JAK / STAT (janus kinase / signal transducer and activator of transcription protein) or MAPK (mitogen-activated protein kinase) signaling cascades.…”

“…Studies have found an increase in sIL-6R levels in the blood and sputum of COPD patients [18] that indicates its important pathological role in this disease. It has reported that IL-6 provides for the recruitment of innate immunity cells in inflammatory focus in COPD by activating chemokine synthesis in endothelial cells via trans-signaling [9]. Le et.…”

“…According to modern concepts, the biolog cal effects of IL-6 largely depend on signal pathway. There are two main types of IL-6 signaling: classical and trans-signaling [9]. Data on IL-6 classical signaling at different stages of COPD are absent.…”

The role of cytokines in the development of systemic inflammation in chronic obstructive pulmonary disease and obesity

“…Повышенная концентрация IL-6 у больных ХОБЛ имеет тенденцию к неуклонному росту по мере прогрессирования ХОБЛ. Именно поэтому IL-6 является маркером системного воспаления [30,31]. Поскольку IL-6 является цитокином, обладающим, помимо про-, еще и противовоспалительными свойствами, его молекулярная активность достигается путем взаимодействия со специальным рецепторным комплексом, состоящим из двух субъединиц: IL-6R и gp130.…”

“…Результат реакции IL-6 с эф-фекторной клеткой напрямую зависит от типа сигналинга. В настоящее время известно три механизма передачи сигнала в клетку мишень: классический, кластерный и транссигналинг [29][30][31][32][33].…”