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

Patients with chronic obstructive pulmonary disease (COPD) are characterized by a variety of comorbid conditions, including both somatic (arterial hypertension, atherosclerosis, coronary heart disease, bronchial asthma, malignant  neoplasms, diabetes mellitus, obesity, etc.) and mental (depressive disorders, suicide attempts). Against the background  of various chronic diseases of the respiratory system, endocrine, metabolic disorders, the risks of exacerbations of COPD increase.

The leading  unifying  mechanism  of these conditions  is systemic subclinical  inflammation. Its excessive activity leads to the loss of the physiological functions of inflammation, which is accompanied  by an imbalance  in the endocrine system and the release of high concentrations of hormones and neurotransmitters. The result of this response is the uncoupling of cytokine mechanisms, which leads to an imbalance in the system of pro- and anti-inflammatory cytokines.

The article describes the role of the pro-inflammatory chemokine  IL-8 (interleukin 8), which is responsible for the migration of neutrophils to the site of inflammation. This is how the neutrophilic type of inflammation is formed. IL-4 and IL-10 are considered, which occupy a leading position in the formation of CD4+ type of immunoreactivity, which is observed in bronchial asthma. Attention is focused on the significance of IL-6, because it is an integral component of local and systemic inflammation. An increase in its concentration and, as a result, a potential risk of damage to the respiratory epithelium is the remodeling of the bronchial tree, resulting in a decrease in the elasticity of the epithelium of the respiratory tract. This mechanism leads to the formation of pulmonary emphysema and further potentiation of pathophysiological processes in patients with COPD.

Since IL-6 is a cytokine with anti-inflammatory  properties, its molecular activity is achieved by interacting  with a special receptor complex consisting  of two subunits: IL-6R and gp130. The former mediates IL-6 binding, while the latter triggers the JAK/STAT or MAPK signaling  cascade pathways. The result of the reaction of IL-6 with the effector cell directly depends on the type of signaling.

The paper describes three mechanisms of signal transduction into the target cell: classical, cluster, and transsignaling.

Thus, by studying  the role of cytokines in the systemic inflammatory response, we have shown the cross-talk between adipose tissue and the lungs in obesity, highlighting the main inflammatory mediators, which may indicate new therapeutic targets for preventing pulmonary dysfunction.

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