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Open Access 01-12-2019 | Smoking and Nicotine Detoxification | Research

Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD)

Authors: Amit R Agarwal, Smita Kadam, Ankita Brahme, Manas Agrawal, Komalkirti Apte, Govinda Narke, Kushal Kekan, Sapna Madas, Sundeep Salvi

Published in: Respiratory Research | Issue 1/2019

Abstract

Background

Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects.

Methods

PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs’ cycle substrate) was measured using the XFp Extracellular Flux Analyzer. Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry. RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied. Patient’s data was analyzed using the Mann Whitney U test, whereas Student’s t test was performed to analyze the in-vitro data.

Results

PBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%). Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV₁ (r = 0.74, p < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed. The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α. In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate.

Conclusions

These findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease.

Trial registration

This observational study was retrospectively registered in the Clinical Trails Registry – India (ICMR – NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441.

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Title: Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD)
Authors: Amit R Agarwal
Smita Kadam
Ankita Brahme
Manas Agrawal
Komalkirti Apte
Govinda Narke
Kushal Kekan
Sapna Madas
Sundeep Salvi
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Smoking and Nicotine Detoxification
Chronic Obstructive Lung Disease
Published in: Respiratory Research / Issue 1/2019
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-019-1139-2

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