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NK cell immunesenescence is increased by psychological but not physical stress in older adults associated with raised cortisol and reduced perforin expression.

Duggal NA, Upton J, Phillips AC, Hampson P, Lord JM - Age (Dordr) (2015)

Bottom Line: NKCC remained lower in the depressed patients compared to those without depression 6 months post-fracture (p = 0.017).Serum cortisol levels were also elevated in patients with depression compared to non-depressed patients at 6 weeks (p = 0.01) and 6 months (p = 0.05).NK cells treated with dexamethasone showed a concentration-dependent reduction in NKCC and perforin expression.

View Article: PubMed Central - PubMed

Affiliation: MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

ABSTRACT
NK cell cytotoxicity (NKCC) reduces with age and this has been associated previously with increased mortality. The immune response is also modulated by stress, and here, we assessed the effect of the physical stress of hip fracture and the psychological stress of depression on NKCC in an aged immune system. NKCC was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and in 50 healthy age-matched controls (28 female). Thirty-eight patients were depressed at 6 weeks post-injury, and NKCC was reduced in patients who developed depression compared with non-depressed hip fracture patients (p = 0.004) or controls (p < 0.02). NKCC remained lower in the depressed patients compared to those without depression 6 months post-fracture (p = 0.017). We found reduced expression of perforin in NK cells of depressed hip fracture patients compared with controls at 6 weeks (p = 0.001) post-fracture. Serum cortisol levels were also elevated in patients with depression compared to non-depressed patients at 6 weeks (p = 0.01) and 6 months (p = 0.05). NK cells treated with dexamethasone showed a concentration-dependent reduction in NKCC and perforin expression. We propose that depression is the major factor affecting NK cell immunity after hip fracture.

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Related in: MedlinePlus

Relationship of serum cortisol to NKCC. Serum cortisol for healthy controls (n = 34) and hip fracture patients (n = 64) were correlated with values for NKCC
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Fig3: Relationship of serum cortisol to NKCC. Serum cortisol for healthy controls (n = 34) and hip fracture patients (n = 64) were correlated with values for NKCC

Mentions: Analysis of cortisol levels after 6 weeks revealed significantly higher serum cortisol levels in hip fracture patients with depressive symptoms (0.17 ± 0.05 mg/ml) compared with healthy controls (0.13 ± 0.04 mg/ml; p = 0.006) or with hip fracture patients without depression (0.12 ± 0.04 mg/ml; p < 0.001). By 6 months, the cortisol levels were still significantly raised in the depressed group (0.14 ± 0.04 mg/ml) compared with hip fracture patients without depression (0.11 ± 0.03 mg/ml; p < 0.01). Further, a significant association was found between serum cortisol levels and NKCC in hip fracture patients, β = −.25, p = 0.02, ΔR2 = .06 (Fig. 3), but not with NK cell perforin expression (p = 0.76). DHEAS levels were also significantly lower after 6 weeks in hip fracture patients with depressive symptoms (0.17 ± 0.14 mg/ml) compared with healthy controls (0.81 ± 0.36 mg/ml; p < 0.001) and the hip fracture alone group (0.43 ± 0.80 mg/ml; p = 0.008). Also, DHEAS levels of hip fracture patients without depression were significantly lower than healthy controls (p = 0.03). However, serum DHEAS did not relate to NKCC (p = 0.58) or perforin expression (p = 0.30). Also by 6 months after injury serum, DHEAS levels did not significantly differ between hip fracture patients with (0.23 ± 0.22 mg/ml) and without (0.27 ± 0.20 mg/ml) depressive symptoms (p = 0.14).Fig. 3


NK cell immunesenescence is increased by psychological but not physical stress in older adults associated with raised cortisol and reduced perforin expression.

Duggal NA, Upton J, Phillips AC, Hampson P, Lord JM - Age (Dordr) (2015)

Relationship of serum cortisol to NKCC. Serum cortisol for healthy controls (n = 34) and hip fracture patients (n = 64) were correlated with values for NKCC
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4320126&req=5

Fig3: Relationship of serum cortisol to NKCC. Serum cortisol for healthy controls (n = 34) and hip fracture patients (n = 64) were correlated with values for NKCC
Mentions: Analysis of cortisol levels after 6 weeks revealed significantly higher serum cortisol levels in hip fracture patients with depressive symptoms (0.17 ± 0.05 mg/ml) compared with healthy controls (0.13 ± 0.04 mg/ml; p = 0.006) or with hip fracture patients without depression (0.12 ± 0.04 mg/ml; p < 0.001). By 6 months, the cortisol levels were still significantly raised in the depressed group (0.14 ± 0.04 mg/ml) compared with hip fracture patients without depression (0.11 ± 0.03 mg/ml; p < 0.01). Further, a significant association was found between serum cortisol levels and NKCC in hip fracture patients, β = −.25, p = 0.02, ΔR2 = .06 (Fig. 3), but not with NK cell perforin expression (p = 0.76). DHEAS levels were also significantly lower after 6 weeks in hip fracture patients with depressive symptoms (0.17 ± 0.14 mg/ml) compared with healthy controls (0.81 ± 0.36 mg/ml; p < 0.001) and the hip fracture alone group (0.43 ± 0.80 mg/ml; p = 0.008). Also, DHEAS levels of hip fracture patients without depression were significantly lower than healthy controls (p = 0.03). However, serum DHEAS did not relate to NKCC (p = 0.58) or perforin expression (p = 0.30). Also by 6 months after injury serum, DHEAS levels did not significantly differ between hip fracture patients with (0.23 ± 0.22 mg/ml) and without (0.27 ± 0.20 mg/ml) depressive symptoms (p = 0.14).Fig. 3

Bottom Line: NKCC remained lower in the depressed patients compared to those without depression 6 months post-fracture (p = 0.017).Serum cortisol levels were also elevated in patients with depression compared to non-depressed patients at 6 weeks (p = 0.01) and 6 months (p = 0.05).NK cells treated with dexamethasone showed a concentration-dependent reduction in NKCC and perforin expression.

View Article: PubMed Central - PubMed

Affiliation: MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

ABSTRACT
NK cell cytotoxicity (NKCC) reduces with age and this has been associated previously with increased mortality. The immune response is also modulated by stress, and here, we assessed the effect of the physical stress of hip fracture and the psychological stress of depression on NKCC in an aged immune system. NKCC was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and in 50 healthy age-matched controls (28 female). Thirty-eight patients were depressed at 6 weeks post-injury, and NKCC was reduced in patients who developed depression compared with non-depressed hip fracture patients (p = 0.004) or controls (p < 0.02). NKCC remained lower in the depressed patients compared to those without depression 6 months post-fracture (p = 0.017). We found reduced expression of perforin in NK cells of depressed hip fracture patients compared with controls at 6 weeks (p = 0.001) post-fracture. Serum cortisol levels were also elevated in patients with depression compared to non-depressed patients at 6 weeks (p = 0.01) and 6 months (p = 0.05). NK cells treated with dexamethasone showed a concentration-dependent reduction in NKCC and perforin expression. We propose that depression is the major factor affecting NK cell immunity after hip fracture.

Show MeSH
Related in: MedlinePlus