Inflammatory Response, Sepsis
Conditions
Keywords
sepsis, CD8+ T cell, central memory CD8+ T cell, inflammatory response
Brief summary
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis. Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice. This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.
Interventions
None listed
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Patients aged 18-60 years old without restriction of gender, race, religion, creed or nationality; No sedative drugs with elimination half-life were used before inclusion in the study; Patients and/or their family members know and agree to participate in the trial.
Exclusion criteria
History of solid organ or bone marrow transplantation; Diseases that may affect immune-related indicators, such as autoimmune diseases such as rheumatoid arthritis and SLE, or hematological malignancies such as leukemia and lymphoma; Have received radiotherapy or chemotherapy within the past 30 days, or have received immunosuppressive drugs (tripterygium, mycophenolate, cyclophosphamide, FK506, etc); Pregnancy or lactation; Chronic nephrosis; Severe chronic liver disease (child-Pugh: Grade C); alcohol or opioid dependence, mental illness, or severe cognitive impairment; Patients and/or their family members refuse to participate in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute number of CD8+T subsets in the peripheral blood (0 hour) | 0 hour after study inclusion | CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells |
| Absolute number of CD8+T subsets in the peripheral blood (24 hours) | 24 hours after study inclusion | CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells |
| Absolute number of CD8+T subsets in the peripheral blood (48 hours) | 48 hours after study inclusion | CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells |
| Absolute number of CD8+T subsets in the peripheral blood (72 hours) | 72 hours after study inclusion | CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells |
| proliferation of CD8+T subsets in the peripheral blood (0 hour) | 0 hour after study inclusion | expression of Ki67 in Tcm and Tem |
| proliferation of CD8+T subsets in the peripheral blood (24 hours) | 24 hours after study inclusion | expression of Ki67 in Tcm and Tem |
| proliferation of CD8+T subsets in the peripheral blood (48 hours) | 48 hours after study inclusion | expression of Ki67 in Tcm and Tem |
| proliferation of CD8+T subsets in the peripheral blood (72 hours) | 72 hours after study inclusion | expression of Ki67 in Tcm and Tem |
| ICU length of stay | up to 4 weeks | Length of stay in the ICU |
| PD-1 expression of CD8+T subsets in the peripheral blood (24 hours) | 24 hours after study inclusion | expression of PD-1 in Tcm and Tem |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mechanical ventilation time after inclusion | up to 4 weeks | Patients requiring mechanical ventilation after study inclusion |
| Total hospital length of stay | up to 4 weeks | Total length of hospital stay |
| In-hospital mortality | up to 4 weeks | Mortality rates for the entire period of hospitalization |
| 90-day readmission rate | up to 4 weeks | Percentage of readmission to hospital within 90 days of study inclusion |
| Infection complications | up to 4 weeks | Pulmonary infection, urinary tract infection, bloodstream infections, etc |
| Acute physiology and chronic health evaluation (APACHE) Ⅱ score | 0h after study inclusion | 0-67, higher scores correspond to more severe disease and a higher risk of death |
| Sequential organ failure assessment (SOFA) score | 0 hour after study inclusion | 0-43, higher scores correspond to more severe sepsis |
| Plasma cytokine levels | 0 hour after study inclusion | IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α |
| Peripheral blood PMN-MDSC levels | Within 72 hours of sepsis diagnosis or ICU admission. | Frequencies and absolute numbers of total PMN-MDSCs (CD45⁺ CD11b⁺ CD15⁺ CD14- CD33⁺ HLA-DRˡᵒʷ) and the CXCR2⁺ PD-L1⁺ PMN-MDSC subpopulation, assessed via flow cytometry. |
Countries
China
Outcome results
None listed