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Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM - PLoS ONE (2014)

Bottom Line: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs).Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Whether these changes contribute to or are caused by these conditions warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Background: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results: The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions: These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

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Related in: MedlinePlus

Cytokine production, but not induction, is elevated in monocytes from the advanced-age, frail elderly as compared to young adults.PBMCs were stimulated with mock (PBS), and TLR-2 (Pam3CSK4, Pam) and TLR-4 (LPS) agonists, and the production of A) IL-1β, B) IL-6, C) IL-8 and D) TNF in classical (CLS), intermediate (INT) and non-classical (NON) monocytes was measured by flow cytometry. Relative to mock, the induction of E) TNF was significantly lower in the advanced-age, frail elderly. n = 5–8 per group, per treatment. Comparison-wise p-value, ***p<0.001, **p<0.01, *p<0.05.
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pone-0104522-g002: Cytokine production, but not induction, is elevated in monocytes from the advanced-age, frail elderly as compared to young adults.PBMCs were stimulated with mock (PBS), and TLR-2 (Pam3CSK4, Pam) and TLR-4 (LPS) agonists, and the production of A) IL-1β, B) IL-6, C) IL-8 and D) TNF in classical (CLS), intermediate (INT) and non-classical (NON) monocytes was measured by flow cytometry. Relative to mock, the induction of E) TNF was significantly lower in the advanced-age, frail elderly. n = 5–8 per group, per treatment. Comparison-wise p-value, ***p<0.001, **p<0.01, *p<0.05.

Mentions: Although only subtle differences in the expression of TLR-2 and -4 were observed for monocytes from the advanced-age, frail elderly, we sought to additionally characterize the functional capacity of monocyte subsets from this age group to respond to stimulus via these receptors. Using intracellular cytokine staining, the production of IL-1β, IL-6, IL-8 and TNF by monocytes subsets in response to Pam3CSK4 (TLR-2 agonist) and LPS (TLR-4 agonist) were quantified in PBMCs from the advanced-age, frail elderly and young adults. Consistent with previous literature [11], [15], [16] the relative production of cytokine by monocyte subsets are as follows: IL-1β, Classical  =  Intermediate > Non-classical; IL-6, Intermediate > Classical > Non-classical; IL-8, Classical  =  Intermediate > Non-classical; TNF, Intermediate ≥ Non-classical > Classical (Figure 2A-D). No significant differences between age-groups in the overall production of IL-1β (Figure 2A) or IL-6 (Figure 2B) were observed. Classical monocytes from the advanced-age, frail elderly produced more IL-8 in response to LPS as compared to young adults (Figure 2D), and for all subsets, with exception to intermediate monocytes stimulated with LPS, TNF production was greater in the advanced-age, frail elderly at baseline (PBS mock control) and in response to Pam3CSK4 or LPS (Figure 2D). Interestingly, while the overall production of TNF was greater in the advanced-age, frail elderly, the relative induction of TNF (versus PBS mock control) was significantly lower for all subsets compared to young adults (Figure 2E). No differences between age-groups were observed for the relative induction of IL-1β, IL-6 or IL-8 (data not shown).


Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM - PLoS ONE (2014)

Cytokine production, but not induction, is elevated in monocytes from the advanced-age, frail elderly as compared to young adults.PBMCs were stimulated with mock (PBS), and TLR-2 (Pam3CSK4, Pam) and TLR-4 (LPS) agonists, and the production of A) IL-1β, B) IL-6, C) IL-8 and D) TNF in classical (CLS), intermediate (INT) and non-classical (NON) monocytes was measured by flow cytometry. Relative to mock, the induction of E) TNF was significantly lower in the advanced-age, frail elderly. n = 5–8 per group, per treatment. Comparison-wise p-value, ***p<0.001, **p<0.01, *p<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126708&req=5

pone-0104522-g002: Cytokine production, but not induction, is elevated in monocytes from the advanced-age, frail elderly as compared to young adults.PBMCs were stimulated with mock (PBS), and TLR-2 (Pam3CSK4, Pam) and TLR-4 (LPS) agonists, and the production of A) IL-1β, B) IL-6, C) IL-8 and D) TNF in classical (CLS), intermediate (INT) and non-classical (NON) monocytes was measured by flow cytometry. Relative to mock, the induction of E) TNF was significantly lower in the advanced-age, frail elderly. n = 5–8 per group, per treatment. Comparison-wise p-value, ***p<0.001, **p<0.01, *p<0.05.
Mentions: Although only subtle differences in the expression of TLR-2 and -4 were observed for monocytes from the advanced-age, frail elderly, we sought to additionally characterize the functional capacity of monocyte subsets from this age group to respond to stimulus via these receptors. Using intracellular cytokine staining, the production of IL-1β, IL-6, IL-8 and TNF by monocytes subsets in response to Pam3CSK4 (TLR-2 agonist) and LPS (TLR-4 agonist) were quantified in PBMCs from the advanced-age, frail elderly and young adults. Consistent with previous literature [11], [15], [16] the relative production of cytokine by monocyte subsets are as follows: IL-1β, Classical  =  Intermediate > Non-classical; IL-6, Intermediate > Classical > Non-classical; IL-8, Classical  =  Intermediate > Non-classical; TNF, Intermediate ≥ Non-classical > Classical (Figure 2A-D). No significant differences between age-groups in the overall production of IL-1β (Figure 2A) or IL-6 (Figure 2B) were observed. Classical monocytes from the advanced-age, frail elderly produced more IL-8 in response to LPS as compared to young adults (Figure 2D), and for all subsets, with exception to intermediate monocytes stimulated with LPS, TNF production was greater in the advanced-age, frail elderly at baseline (PBS mock control) and in response to Pam3CSK4 or LPS (Figure 2D). Interestingly, while the overall production of TNF was greater in the advanced-age, frail elderly, the relative induction of TNF (versus PBS mock control) was significantly lower for all subsets compared to young adults (Figure 2E). No differences between age-groups were observed for the relative induction of IL-1β, IL-6 or IL-8 (data not shown).

Bottom Line: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs).Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Whether these changes contribute to or are caused by these conditions warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Background: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results: The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions: These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

Show MeSH
Related in: MedlinePlus