title: The links between chronic obstructive pulmonary disease and comorbid depressive symptoms: role of IL-2 and IFN-γ.
abstract: Depression is highly prevalent in COPD patients, and both diseases are believed to be associated with inflammation. The aim of this study was to elucidate the role of the immune system alterations in pathogenesis of depression in COPD patients. Blood was collected from patients diagnosed with chronic obstructive pulmonary disease and comorbid depressive symptoms [COPD + DS, (N = 13)], from individuals with either COPD (N = 16) or recurrent depressive disorder (rDD) alone (N = 15), and from healthy controls (N = 19). Surface phenotype expression of T regulatory and T effector cells was analyzed with a flow cytometry, and IL-2, IL-6, IL-8, IFN-γ, IL-17, and neopterin were detected with ELISA. We demonstrated that COPD, depression, and COPD with comorbid depression are associated with increased IL-6 levels when compared with healthy controls 42.2 ± 1.87, 40.9 ± 2.12, 41.7 ± 1.31, and 33.2 ± 1.23 pg/ml, respectively (p < 0.05). A significant increase in neopterin levels was observed both in rDD and COPD patients when compared with controls (15.69 ± 0.095, 13.98 ± 0.887 vs. 9.22 ± 0.466 nmol/l, p < 0.001 and p < 0.05, respectively). Concentrations of IFN-γ were significantly increased in COPD + DS patients when compared with controls (24.3 ± 1.49 and 17.8 ± 0.70 pg/ml, respectively, p < 0.05). IL-2 levels were highest in COPD + DS (3.20 ± 0.389 pg/ml) and differed significantly when this group was compared with controls (2.20 ± 0.184 pg/ml), p ≤ 0.05). In this study, we demonstrated for the first time that depressive symptoms in COPD patients may be related to inflammatory state as confirmed by increased levels of IL-6 both in COPD and depression and also in COPD with comorbid depressive symptoms, despite the fact that the patients were treated with anti-inflammatory drugs and/or antidepressants. We also identified IFN-γ and IL-2 as putative inflammatory agents associated with depressive symptoms in COPD patients. Prospective studies will need to confirm whether measuring IL-2 and IFN-γ can identify COPD patients at risk of depression. These findings suggest that T helper cell 1-derived cellular immune activation may play significant role in developing depressive symptoms in COPD patients.
authors.affiliation: Department and Clinic of Geriatrics, Collegium Medicum UMK in Bydgoszcz, M. Curie Skłodowska St. 9, 85-094, Bydgoszcz, Poland. joanna.rybka1@wp.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rybka
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
authors.forename: S Mechiel
authors.initials: SM
authors.lastname: Korte
authors.affiliation: Department of Lung Diseases and Respiratory Failure, Kujawsko-Pomorskie Pneumonology Centre, Bydgoszcz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Czajkowska-Malinowska
authors.affiliation: Department of Immunology (Faculty of Pharmacy), Collegium Medicum UMK in Bydgoszcz, Bydgoszcz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Wiese
authors.affiliation: Department and Clinic of Geriatrics, Collegium Medicum UMK in Bydgoszcz, M. Curie Skłodowska St. 9, 85-094, Bydgoszcz, Poland.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Kędziora-Kornatowska
authors.affiliation: Collegium Medicum UMK in Bydgoszcz, Bydgoszcz, Poland.
authors.forename: Józef
authors.initials: J
authors.lastname: Kędziora
mesh_terms: D015897:Comorbidity; D003863:Depression / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000378:metabolism; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000523:psychology; D018417:Th1 Cells / Q000276:immunology
chemical_list: C573415:IFNG protein, human; C508594:IL2 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; D019798:Neopterin; D007371:Interferon-gamma
keywords: COPD; Depression; IFN-γ; IL-2; IL-6; Neopterin; Treg