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Persistent inflammation and T cell exhaustion in severe sepsis in the elderly.

Inoue S, Suzuki K, Komori Y, Morishita Y, Suzuki-Utsunomiya K, Hozumi K, Inokuchi S, Sato T - Crit Care (2014)

Bottom Line: Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥ 65 years) and adult (18-64 years) septic patients with serial measurement of serum interleukin (IL)-6.Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation.Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis.

Methods: Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥ 65 years) and adult (18-64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6-8 weeks) and aged (20-22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured.

Results: The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P < 0.05). Serum IL-6 levels in elderly sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P < 0.01). Ex vivo stimulation decreased CD25 expression, IL-2 production, and proliferation to a greater extent in CD4+ T cells from elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased detection of gram-negative bacteria at days 14-16 and 28-32 after sepsis (P < 0.05).

Conclusions: Persistent inflammation and T cell exhaustion may be associated with decreased survival in elderly patients and mice after sepsis.

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Related in: MedlinePlus

Increased population of neutrophils and macrophages in peripheral blood and lymph nodes of aged mice. (A) Neutrophils and monocytes in the peripheral blood of adult and elderly cohorts were counted by an automated hematology analyzer; n = 14 to 40 per group, *P <0.05. (B) Populations of neutrophils (Gr1+/CD11b+) and monocytes (F4/80+) in peripheral blood and mesenteric lymph nodes from CLP- and sham-treated mice were identified by flow cytometric analysis; n = 10 to 12 per group, **P <0.01, *P <0.05.
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Figure 3: Increased population of neutrophils and macrophages in peripheral blood and lymph nodes of aged mice. (A) Neutrophils and monocytes in the peripheral blood of adult and elderly cohorts were counted by an automated hematology analyzer; n = 14 to 40 per group, *P <0.05. (B) Populations of neutrophils (Gr1+/CD11b+) and monocytes (F4/80+) in peripheral blood and mesenteric lymph nodes from CLP- and sham-treated mice were identified by flow cytometric analysis; n = 10 to 12 per group, **P <0.01, *P <0.05.

Mentions: Sepsis induced a significant increase in circulating neutrophils and monocytes in both adult and elderly patients within 24 h after diagnosis, without a significant difference between adult and elderly patients (P <0.01; Figure 3A). In contrast to the human cohort, aged mice demonstrated an increased number of neutrophils and macrophages in both the peripheral blood and lymph nodes relative to young mice (Figure 3B).


Persistent inflammation and T cell exhaustion in severe sepsis in the elderly.

Inoue S, Suzuki K, Komori Y, Morishita Y, Suzuki-Utsunomiya K, Hozumi K, Inokuchi S, Sato T - Crit Care (2014)

Increased population of neutrophils and macrophages in peripheral blood and lymph nodes of aged mice. (A) Neutrophils and monocytes in the peripheral blood of adult and elderly cohorts were counted by an automated hematology analyzer; n = 14 to 40 per group, *P <0.05. (B) Populations of neutrophils (Gr1+/CD11b+) and monocytes (F4/80+) in peripheral blood and mesenteric lymph nodes from CLP- and sham-treated mice were identified by flow cytometric analysis; n = 10 to 12 per group, **P <0.01, *P <0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230031&req=5

Figure 3: Increased population of neutrophils and macrophages in peripheral blood and lymph nodes of aged mice. (A) Neutrophils and monocytes in the peripheral blood of adult and elderly cohorts were counted by an automated hematology analyzer; n = 14 to 40 per group, *P <0.05. (B) Populations of neutrophils (Gr1+/CD11b+) and monocytes (F4/80+) in peripheral blood and mesenteric lymph nodes from CLP- and sham-treated mice were identified by flow cytometric analysis; n = 10 to 12 per group, **P <0.01, *P <0.05.
Mentions: Sepsis induced a significant increase in circulating neutrophils and monocytes in both adult and elderly patients within 24 h after diagnosis, without a significant difference between adult and elderly patients (P <0.01; Figure 3A). In contrast to the human cohort, aged mice demonstrated an increased number of neutrophils and macrophages in both the peripheral blood and lymph nodes relative to young mice (Figure 3B).

Bottom Line: Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥ 65 years) and adult (18-64 years) septic patients with serial measurement of serum interleukin (IL)-6.Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation.Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis.

Methods: Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥ 65 years) and adult (18-64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6-8 weeks) and aged (20-22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured.

Results: The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P < 0.05). Serum IL-6 levels in elderly sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P < 0.01). Ex vivo stimulation decreased CD25 expression, IL-2 production, and proliferation to a greater extent in CD4+ T cells from elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased detection of gram-negative bacteria at days 14-16 and 28-32 after sepsis (P < 0.05).

Conclusions: Persistent inflammation and T cell exhaustion may be associated with decreased survival in elderly patients and mice after sepsis.

Show MeSH
Related in: MedlinePlus