1. Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD
- Author
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Jameel, Kaschin Jamal, Gallert, Willem-Jakob, Yanik, Sarah D., Panek, Susanne, Kronsbein, Juliane, Jungck, David, Koch, Andrea, and Knobloch, Jürgen
- Subjects
Male ,Smokers ,QH301-705.5 ,T-Lymphocytes ,T-cells ,Smoking ,Comorbidity ,Middle Aged ,comorbidities ,Article ,Pulmonary Disease, Chronic Obstructive ,Chemistry ,Case-Control Studies ,Germany ,Cytokines ,Humans ,COPD ,Female ,ddc:610 ,Biology (General) ,QD1-999 ,Biomarkers - Abstract
In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total n = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP, chemokine (C-C motif) ligand 18, CCL18, C-X3-C motif chemokine ligand 1, CX3CL1, interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22, epidermal growth factor, EGF, IL-17, periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFNγ and TNFα without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma— and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations.
- Published
- 2021