title: Persistent inflammation and T cell exhaustion in severe sepsis in the elderly.
abstract: BACKGROUND
  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.
authors: Shigeaki
authors: S
authors: Inoue
authors: Kodai
authors: K
authors: Suzuki
authors: Yukako
authors: Y
authors: Komori
authors: Yukiko
authors: Y
authors: Morishita
authors: Kyoko
authors: K
authors: Suzuki-Utsunomiya
authors: Katsuto
authors: K
authors: Hozumi
authors: Sadaki
authors: S
authors: Inokuchi
authors: Takehito
authors: T
authors: Sato
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008264:Macrophages; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009504:Neutrophils; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology*; D012709:Serum Albumin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; D012709:Serum Albumin