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Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study.

Huang LF, Yao YM, Dong N, Yu Y, He LX, Sheng ZY - Crit Care (2010)

Bottom Line: They were also higher in septic patients than those without sepsis.Among septic patients, the expressions of Tregs phenotypes and the levels of cytokines were markedly lower in the survival group than those in patients with fatal outcome.Severe burn injury per se could lead to the changes in Tregs activities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, 51 Fu-cheng Road, Haidian District, Beijing 100048, PR China. burnshlf@sina.com

ABSTRACT

Introduction: To investigate the significance of changes in regulatory T cells (Tregs) activity and its relationship with sepsis, as well as outcome of patients with major burns.

Methods: The periphery blood samples of 106 patients were collected on post-burn days 1, 3, 7, 14, and 21. Tregs were isolated and their phenotypes (cytotoxic T-lymphocyte-associated antigen 4 and forkhead/winged helix transcription factor p3) were analyzed by flow cytometry, and the contents of cytokines (interleukin-10 and transforming growth factor-beta1) released into supernatants by Tregs were also determined by enzyme-linked immunosorbent assay kits. Gene expressions of cytokines were assessed by real-time quantitative polymerase chain reaction.

Results: Expressions of Tregs phenotypes and gene/protein expression of cytokines were all elevated after burn, and there were obvious differences among patients with various burn sizes. They were also higher in septic patients than those without sepsis. Among septic patients, the expressions of Tregs phenotypes and the levels of cytokines were markedly lower in the survival group than those in patients with fatal outcome.

Conclusions: Severe burn injury per se could lead to the changes in Tregs activities. Elevated levels of cytokines produced by Tregs and activation markers on Tregs surface might play an important role in the pathogenesis of sepsis and mortality in burned patients.

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Flow cytometric analysis of phenotypes of Tregs. Increased expressions of CTLA-4 and FOXP3 on the surface of regulatory T cells (Tregs) from burned patients were found on postburn days (PBD) 1 to 21 compared with normal controls, and there were obvious differences among patients with various burn sizes ((a and b) a mean of all days). The expressions of CTLA-4 and FOXP3 were significantly higher in patients with serious burns during the whole observational period, and (c and d) they were much higher in septic patients than those without sepsis on PBD 3 to 21. (e and f) Among septic patients, the expressions of CTLA-4 and FOXP3 in the survival group were obviously lower than those in non-survival group on PBD 3 to 21. * P < 0.05, ** P < 0.01, Group I vs. normal group or sepsis group vs. non-sepsis group or non-survivors vs. survivors; #P < 0.05, ## P < 0.01, Group II vs. Group I; &P < 0.05, Group III vs. Group II.
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Figure 2: Flow cytometric analysis of phenotypes of Tregs. Increased expressions of CTLA-4 and FOXP3 on the surface of regulatory T cells (Tregs) from burned patients were found on postburn days (PBD) 1 to 21 compared with normal controls, and there were obvious differences among patients with various burn sizes ((a and b) a mean of all days). The expressions of CTLA-4 and FOXP3 were significantly higher in patients with serious burns during the whole observational period, and (c and d) they were much higher in septic patients than those without sepsis on PBD 3 to 21. (e and f) Among septic patients, the expressions of CTLA-4 and FOXP3 in the survival group were obviously lower than those in non-survival group on PBD 3 to 21. * P < 0.05, ** P < 0.01, Group I vs. normal group or sepsis group vs. non-sepsis group or non-survivors vs. survivors; #P < 0.05, ## P < 0.01, Group II vs. Group I; &P < 0.05, Group III vs. Group II.

Mentions: To investigate the changes in Treg phenotypes, these cells were analyzed at different time points and in different groups after burns. A three (Group) times five (Day) mixed-model, factorial ANOVA was conducted. As shown in Figure 2, increased expressions of CTLA-4 and FOXP3 were found to be enhanced on the surface of Tregs from burned patients on PBD 1 to 21 compared with normal controls, and there were obvious differences among patients with various burn sizes (P < 0.05 or P < 0.01). The expressions of CTLA-4 and FOXP3 were significantly higher in patients with serious burns at all time points, and they were even higher in septic patients than those without sepsis on PBD 3 to 21 (P < 0.01). Among septic patients, the expressions of CTLA-4 and FOXP3 in the survival group were significantly lower than those with fatal outcome on PBD 3 to 21 (P < 0.05 or P < 0.01).


Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study.

Huang LF, Yao YM, Dong N, Yu Y, He LX, Sheng ZY - Crit Care (2010)

Flow cytometric analysis of phenotypes of Tregs. Increased expressions of CTLA-4 and FOXP3 on the surface of regulatory T cells (Tregs) from burned patients were found on postburn days (PBD) 1 to 21 compared with normal controls, and there were obvious differences among patients with various burn sizes ((a and b) a mean of all days). The expressions of CTLA-4 and FOXP3 were significantly higher in patients with serious burns during the whole observational period, and (c and d) they were much higher in septic patients than those without sepsis on PBD 3 to 21. (e and f) Among septic patients, the expressions of CTLA-4 and FOXP3 in the survival group were obviously lower than those in non-survival group on PBD 3 to 21. * P < 0.05, ** P < 0.01, Group I vs. normal group or sepsis group vs. non-sepsis group or non-survivors vs. survivors; #P < 0.05, ## P < 0.01, Group II vs. Group I; &P < 0.05, Group III vs. Group II.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875505&req=5

Figure 2: Flow cytometric analysis of phenotypes of Tregs. Increased expressions of CTLA-4 and FOXP3 on the surface of regulatory T cells (Tregs) from burned patients were found on postburn days (PBD) 1 to 21 compared with normal controls, and there were obvious differences among patients with various burn sizes ((a and b) a mean of all days). The expressions of CTLA-4 and FOXP3 were significantly higher in patients with serious burns during the whole observational period, and (c and d) they were much higher in septic patients than those without sepsis on PBD 3 to 21. (e and f) Among septic patients, the expressions of CTLA-4 and FOXP3 in the survival group were obviously lower than those in non-survival group on PBD 3 to 21. * P < 0.05, ** P < 0.01, Group I vs. normal group or sepsis group vs. non-sepsis group or non-survivors vs. survivors; #P < 0.05, ## P < 0.01, Group II vs. Group I; &P < 0.05, Group III vs. Group II.
Mentions: To investigate the changes in Treg phenotypes, these cells were analyzed at different time points and in different groups after burns. A three (Group) times five (Day) mixed-model, factorial ANOVA was conducted. As shown in Figure 2, increased expressions of CTLA-4 and FOXP3 were found to be enhanced on the surface of Tregs from burned patients on PBD 1 to 21 compared with normal controls, and there were obvious differences among patients with various burn sizes (P < 0.05 or P < 0.01). The expressions of CTLA-4 and FOXP3 were significantly higher in patients with serious burns at all time points, and they were even higher in septic patients than those without sepsis on PBD 3 to 21 (P < 0.01). Among septic patients, the expressions of CTLA-4 and FOXP3 in the survival group were significantly lower than those with fatal outcome on PBD 3 to 21 (P < 0.05 or P < 0.01).

Bottom Line: They were also higher in septic patients than those without sepsis.Among septic patients, the expressions of Tregs phenotypes and the levels of cytokines were markedly lower in the survival group than those in patients with fatal outcome.Severe burn injury per se could lead to the changes in Tregs activities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, 51 Fu-cheng Road, Haidian District, Beijing 100048, PR China. burnshlf@sina.com

ABSTRACT

Introduction: To investigate the significance of changes in regulatory T cells (Tregs) activity and its relationship with sepsis, as well as outcome of patients with major burns.

Methods: The periphery blood samples of 106 patients were collected on post-burn days 1, 3, 7, 14, and 21. Tregs were isolated and their phenotypes (cytotoxic T-lymphocyte-associated antigen 4 and forkhead/winged helix transcription factor p3) were analyzed by flow cytometry, and the contents of cytokines (interleukin-10 and transforming growth factor-beta1) released into supernatants by Tregs were also determined by enzyme-linked immunosorbent assay kits. Gene expressions of cytokines were assessed by real-time quantitative polymerase chain reaction.

Results: Expressions of Tregs phenotypes and gene/protein expression of cytokines were all elevated after burn, and there were obvious differences among patients with various burn sizes. They were also higher in septic patients than those without sepsis. Among septic patients, the expressions of Tregs phenotypes and the levels of cytokines were markedly lower in the survival group than those in patients with fatal outcome.

Conclusions: Severe burn injury per se could lead to the changes in Tregs activities. Elevated levels of cytokines produced by Tregs and activation markers on Tregs surface might play an important role in the pathogenesis of sepsis and mortality in burned patients.

Show MeSH
Related in: MedlinePlus