Development of depressive symptoms post hip fracture is associated with altered immunosuppressive phenotype in regulatory T and B lymphocytes - PubMed (original) (raw)

Development of depressive symptoms post hip fracture is associated with altered immunosuppressive phenotype in regulatory T and B lymphocytes

Niharika Arora Duggal et al. Biogerontology. 2016 Feb.

Abstract

Hip fracture is a common physical trauma in older adults that is also associated with a high incidence of new onset depression. The immune system declines with age and is also compromised by physical and psychological stress. This study examined whether hip fracture and depressive symptoms had additive effects upon the aged immune system that might contribute to poor health outcomes after hip fracture. We assessed the frequency of regulatory T cells, Tregs (CD4(+) CD25(+) Foxp3(+)) and IL10 production by CD4 T cells, and the frequency and IL10 production by regulatory B cells, Bregs (CD19(+) CD24(hi) CD38(hi)) in 101 hip fracture patients (81 female) 6 weeks after injury and 43 healthy age-matched controls (28 female). 38 hip fracture patients (37%) developed depressive symptoms. Hip fracture did not have an effect on circulating Tregs frequency but a significant reduction in the frequency of Bregs was observed in patients who developed depression compared with non-depressed patients (p = 0.001) or healthy controls (p < 0.001). Bregs also showed a significant decline in IL10 production in depressed hip fracture patients compared with controls (p = 0.04) and non-depressed patients (p = 0.01). In contrast, there was an increase in IL10 production by CD4 T cells in hip fracture patients with new onset depression compared to hip fracture patients without depression (p = .04) and healthy controls (p = .02). We conclude that the reduced immunity associated with new onset depression post hip fracture could include a contribution by heightened Tregs function.

Keywords: Depression; Hip fracture; Immunesenescence; Regulatory B cell; Regulatory T cell; Stress.

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Figures

Fig. 1

Fig. 1

CD4+ CD25+ Foxp3+ regulatory T lymphocytes in hip fracture patients. a Percentage of CD4+ CD25+ Foxp3+ T cells in healthy controls (n = 20), hip fracture patients without depressive symptoms (HF; n = 20) and hip fracture patients with depressive symptoms (HF + D; n = 20). The solid bar represents the mean value. b Absolute number of CD4+ CD25+ Foxp3+ regulatory T cells in healthy controls (n = 12), hip fracture patients without depressive symptoms (HF; n = 13) and hip fracture patients with depressive symptoms (HF + D; n = 10). Data are mean ± SEM

Fig. 2

Fig. 2

IL10 production by CD4 T lymphocytes in hip fracture patients. a Percentage IL10+ CD4 T cells and b mean IL10 production (MFI value) by CD4 T cells in healthy controls (n = 17), hip fracture patients without depressive symptoms (HF; n = 16) or hip fracture patients with depressive symptoms (HF+D; n = 21). The solid bar represents the mean value in (a) and data are mean ± SEM in (b). c Correlation between GDS depression scores and IL10 production by CD4 T cells in hip fracture patients (n = 36). *p < 0.05

Fig. 3

Fig. 3

Frequency of CD19+CD24hiCD38hi B cells in hip fracture patients. a Percentage and b absolute numbers of CD19+CD24hiCD38hi cells in healthy controls (n = 21), hip fracture patients without depressive symptoms (HF; n = 15) and hip fracture patients with depressive symptoms (HF + D; n = 22). The solid bar represents the mean value in (a) and the data are mean ± SEM in (b). c Correlation between percentage of CD19+CD24hiCD38hi and GDS scores in hip fracture patients (n = 36). *p < 0.05, **p < 0.005 and ***p < 0.001

Fig. 4

Fig. 4

IL10 production by CD19+CD24hiCD38hi B cells in hip fracture patients. a Frequency of IL10+CD19+CD24hiCD38hi cells in healthy controls (n = 18), hip fracture patients without depressive symptoms (HF; n = 21) or hip fracture patients with depressive symptoms (HF+D; n = 19). The solid bar represents the mean value. b IL10 production by CD19+CD24hiCD38hi cells in healthy controls (n = 18), hip fracture patients without depressive symptoms (HF; n = 21) or hip fracture patients with depressive symptoms (HF+D; n = 19) post CD3 stimulation for 72 h. Data are mean ± SEM. c Correlation between percentage of IL10+CD19+CD24hiCD38hi B cells post CD3 stimulation (72 h) and GDS scores in hip fracture patients (n = 40). d IL10 production by CD19+CD24hiCD38hi cells in healthy controls (n = 24), hip fracture patients without depressive symptoms (HF; n = 26) or hip fracture patients with depressive symptoms (HF+D; n = 22) post LPS stimulation for 72 h. *p < 0.05

Fig. 5

Fig. 5

Association between serum cortisol and regulatory cell frequency. The frequency of IL10 producing a CD4 T cells and b CD19+CD24hiCD38hi B cells in patients 6 weeks after hip fracture was correlated with the serum cortisol level

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