Blood was collected from patients diagnosed with chronic obstructive pulmonary disease and comorbid depressive symptoms (COPD+DS, (N=13), individuals with either COPD (N=16) or recurrent depressive disorder (rDD) alone (N=15) and from healthy controls (N=19). Levels of IL-2, IL-6, IL-8, IFN-g, TNF-a, IL-17 and GITR were detected with ELISA. Surface phenotype expression of T regulatory and T effector cells was analysed with a flow cytometery.

We observedthat COPD, depression and COPD with comorbid depression are associated with increased IL-6 levels when compared with healthy controls 42.2±1.87 pg/mL, 41.9±1.51 pg/mL, 41.7 ±1.31 and 34.7±1.36 pg/mL, respectively (p<0.05). Concentrations of IFN-g were significantly increased in COPD+DS patients when compared with controls (24.3±1.49 pg/mL 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 (2.30±0.176 pg/mL), p£0.05. GITR was significantly higher in COPD patients (0.332±0.04849) when compared with depressed (0.183±0.0492), when compared with COPD +depressive symptoms (0.194± 0.0357) and also when compared with controls (0.1601±0.0191), all p<0.05. We observed strong significant positive correlation between GITR and IL-2 and also between GITR and IFN-g in the study groups (p<0.001). Further, we checked the ratios of IL- 2/GITR and IFN-g /GITR. We observed significantly increased IL-2/GITR ratio in depressed groups (p<0.01). We also observed strong positive correlation between IL-2/GITR and Treg/Teffector (p<0.001).

In this study we identified GITR and IL-2 as putative inflammatory agents associated with depressive symptoms in COPD patients. Furthermore our study revealed that alterations of IL-2/GITR balance modulate immunological self-tolerance mediated by Treg cells. Our observations suggest that modulation of IL-2/GITR and its effects on T cell population(s)are putative immune pathways contributing to systemic inflammation in depression.