Cytokine profiles of HIV-associated COPD in a Ugandan Cohort

Abstract

Introduction:COPD is a chronic lung condition characterized by irreversible airflow obstruction and encompasses chronic bronchiolitis and emphysema. Cigarette smoking is the predisposing factor in over 50% of cases but more risk factors are increasingly being discovered. These include Biomass gas exposure, air pollution, HIV/AIDS, TB, pesticide exposure, etc. While much is known about the pathogenesis of COPD, a great majority of this data has been generated based on Cigarette smoke induced models of COPD. Thus, this study seeks to investigate the cytokine profiles underlying HIV-associated COPD. Objectives: 1) To profile the cytokines driving inflammation in a rural cohort of COPD patients compared with negative controls. 2) To compare and contract cytokine levels in plasma and sputum of the different study sub-groups (HIV-COPD-, HIV-COPD+, HIV+COPD-, and HIV+COPD+). Methods: Induced sputum and plasma samples from 8 HIV-COPD-, 11 HIV-COPD+, 9HIV+COPD-, & 10 HIV+COPD+ were retrieved, thawed and analyzed using a 48panel Bio-plex pro human assay kit (Bio-Rad Inc). ODs obtained were analyzed using GraphPad Prism 10 and R-studio. Heat map analysis and Box plots were used to compare cytokine levels between groups. Differences in cytokine levels reaching statistical significance (p-value< 0.05) were considered in the analysis.RESULTS: We saw elevation in levels of some but not all pro-inflammatory cytokines in plasma of COPD+ clients compared to COPD-. There was elevation in both Th1 and Th2 cytokines in sputum of HIV+COPD-, HIV-COPD+, and HIV+COPD+ compared to double negative controls. Plasma had generally lower levels of all pro-inflammatory cytokines.CONCLUSION: Our study has demonstrated elevation in cytokine levels of some but not all pro-inflammatory cytokines, particularly, IL-8, IL-1Ra, MIG, RANTES, MIF, and IP-10 in plasma of COPD+ versus COPD negative samples. Sub-group analysis produced mixed results, with elevations of particular cytokines such as IL-4, IL-12p40, PDGF-BB and IL-7 in sputum, but generally lower cytokine levels in plasma compared to negative controls.