Table 1.
Sepsis-induced immunosuppression—association of secreted cytokine concentration with sepsis severity in neonates and adults with sepsis.
| Adult or neonatal GA | Cohort sepsis characteristics (n) and mortality (if applicable) | Time of blood sampling and age at sepsis | Observation in septic cohort | References |
|---|---|---|---|---|
| TNFα | ||||
| Adult | Organ dysfunction during sepsis: 24 - Organ failure recovery by day 4: 11 - Organ failure ongoing: 13 |
Blood samples were taken within 24 h of initial suspicion of sepsis and on hospital days 4 and 6Mean (median) age at sepsis 55 (55) years | Increased TNFα production capacity is associated with organ failure recovery | (51) |
| Adult | Septic shock: 38 - Survivors: 22 - Non-survivors: 16 Mortality within 28 days after diagnosis. Time from sepsis onset not described |
Blood samples were taken on days 1–2, 3–4, 5–7, and 8–15 days following initial suspicion of sepsisMean age at sepsis 64 years (95% CI 59–69) | TNFα levels were increased in non-survivors compared to survivors, but not significantly | (52) |
| Term(GA range 37–42 weeks) | Clinical (n = 10) and confirmed (n = 3) LOS: 13 - Sepsis: 4 - Severe sepsis: 6 - Septic shock: 3 |
Blood sample was taken at initial suspicion of sepsisMedian age at sepsis: 10 days (IQR 7–22 days) | TNFα levels were not associated with sepsis severity | (53) |
| Mix of preterm andTerm(mean GA not described) | Sepsis: 50 (EOS: 41 and LOS: 9) - Survivors: 33 - Non-survivors:17 Non-sepsis inflammation: 50 Controls: 50 Time from sepsis onset to death not described |
Blood samples were taken at sepsis evaluation (time 0) and on days 1 and 2 Age at sepsis not described | TNFα was significantly elevated in non-survivors, compared to survivors, at time 0, but not on days 1 or 2 | (54) |
| Mix of preterm andTerm(mean GA 35.8 ± 4.1) | Confirmed sepsis: 26 (EOS n = 3 and LOS n = 13) - Survivors: 17 - Non-survivors: 9 Controls: 29 Mortality: EOS deaths <2 days: 5 LOS deaths >7 days: 4 Time from sepsis onset to death not described |
Blood samples were taken at sepsis evaluation before antimicrobial therapy (time 0) and on days 3 and 7 Mean (±SD) age at sepsis:EOS 1.9 (±1.1) daysLOS 20.6 (±8.4) days | TNFα significantly increased progressively during sepsis in the non-survivors TNFα significantly decreased progressively during sepsis in the survivors | (55) |
| IL-6 | ||||
| Adult | Septic shock: 20 SIRS: 11 Healthy controls: 10 | Blood sample was taken within 24 h initial suspicion of sepsisAge at septic shock: 68 years | IL-6 levels higher in septic shock than controls. Increased levels of IL-6 were positively associated with IL-10 levels in septic shock, indicating correlation with sepsis severity | (56) |
| Adult | Sepsis:32 - Sepsis: 19 - Septic shock: 13 Healthy controls: 15 |
Blood sample was taken at initial suspicion of sepsisMean age (±SD) at sepsis:70.8 (±12.7) years | Significantly elevated IL-6 levels in septic patients compared to controls Significantly elevated levels in septic shock compared to sepsis without shock | (57) |
| Term(GA range 37–42 weeks) | Clinical (n = 10) and confirmed (n = 3) LOS: 13 - Sepsis: 4 - Severe sepsis: 6 - Septic shock: 3 |
Blood sample was taken within 24 h initial suspicion of sepsisMedian (IQR) age at sepsis:10 (7–22) days | Increased IL-6 levels are associated with septic shock | (53) |
| Mix of preterm andTerm(mean GA 35.8 ± 4.1) | Confirmed sepsis: 26 (EOS n = 13 and LOS n = 13) - Survivors: 17 - Non-survivors: 9 Controls: 29 Mortality: EOS deaths <2 days: 5 LOS deaths >7 days: 4 Time from sepsis onset to death not described |
Blood samples were taken at sepsis evaluation before antimicrobial therapy (time 0) and on days 3 and 7 followingMean (±SD) age at sepsis:EOS 1.9 (±1.1) daysLOS 20.6 (±8.4) days | IL-6 significantly increased progressively during sepsis episode in the non-survivors IL-6 significantly decreased progressively during sepsis episode in the survivors | (55) |
| Mix of preterm andTerm(mean GA not described) | Confirmed sepsis: 50 (EOS n = 41 and LOS n = 9) - Survivors: 33 - Non-survivors: 17 Non-sepsis inflammation: 50 Controls: 50 Time from sepsis onset to death not described |
Blood samples were taken at sepsis evaluation (time 0) and on days 1 and 2 followingAge at sepsis not described | IL-6 was significantly elevated in non-survivors compared to survivors, at time all three timepoints | (54) |
| IL-8 | ||||
| Adult | Septic shock: 20 SIRS: 11 Healthy controls: 10 | Blood sample was taken within 24 h initial suspicion of sepsisAge at septic shock: 68 years | IL-8 levels elevated compared to SIRS and control. Increased levels of IL-8 are positively associated with IL-10 levels in septic shock, indicating correlation with sepsis severity | (56) |
| Term(GA range 37–42 weeks) | Clinical (n = 10) and confirmed (n = 3) LOS: 13 - Sepsis: 4 - Severe sepsis: 6 - Septic shock: 3 |
Blood sample was taken at initial suspicion of sepsisMedian age at sepsis:10 (IQR 7–22) days | Increased IL-8 levels gradually increased with sepsis severity, but not significantly | (53) |
| Mix of preterm andTerm(mean GA 35.8 ± 4.1) | Confirmed sepsis: 26 (EOS n = 13 and LOS n = 13) - Survivors: 17 - Non-survivors: 9 Controls: 29 - Mortality: EOS deaths <2 days: 5 LOS deaths >7 days: 4 Time from sepsis onset to death not described |
Blood samples were taken at sepsis evaluation before antimicrobial therapy (time 0) and on days 3 and 7Mean (±SD) age at: EOS 1.9 (±1.1) daysLOS 20.6 (±8.4) days | IL-8 increased progressively during sepsis episode in the non-survivors (only significantly between time 0 and day 3) IL-8 significantly decreased progressively during sepsis episode in the survivors | (55) |
| Mix of preterm andTerm(mean GA not described) | Sepsis: 50 (EOS n = 41 and LOS n = 9) - Survivors: 33 - Non-survivors:17 Non-sepsis inflammation: 50 Controls: 50 Time from sepsis onset to death not described |
Blood samples were taken at sepsis evaluation (time 0) and on days 1 and 2Age at sepsis not described | IL-8 was significantly elevated in non-survivors compared to survivors, at time all three timepoints | (54) |
| IL-10 | ||||
| Adult | Septic shock: 38 - Survivors: 22 - Non-survivors: 16 Mortality within 28 days after diagnosis. Time from sepsis onset to death not described |
Blood samples were taken on days 1–2, 3–4, 5–7, and 8–15 days following initial suspicion of sepsisMean age at sepsis:64 years (95% CI 59–69) | IL-10 levels were significantly elevated throughout the septic episode in non-survivors compared to survivors | (52) |
| Adult | Infection (includes more than only sepsis): 399 - Survivors: 366 - Non-survivors: 33 Time from sepsis onset to death unclear |
Blood sample was taken when empirical antibiotics commencedMedian (IQR) age at sepsis: 61 (45–77) years | IL-10 levels were significantly higher in the non-survivors. Increased IL-10 levels were associated with increased risk of mortality | (58) |
| Adult | Septic shock: 20 SIRS: 11 Healthy controls: 10 | Blood sample was taken within 24 h initial suspicion of sepsisAge at septic shock: 68 years | IL-10 levels more elevated than controls. Increased levels of IL-6 and IL-8 are positively associated with IL-10 levels in septic shock, indicating correlation with sepsis severity | (56) |
| Adult | Sepsis:32 - Sepsis: 19 - Septic shock: 13 Healthy controls: 15 |
Blood sample was taken at time of initial suspicion of sepsisMean (±SD) age at sepsis:70.8 (±12.7) years | Significantly elevated IL-10 levels in septic patients compared to controls. Significantly elevated levels in septic shock compared to sepsis without shock | (57) |
| Adult | Sepsis: 61 - Survivors: 41 - Non-survivors: 20 Time from sepsis onset to death not described |
Blood sample was taken on day of admission and the next dayMedian (IQR) age at sepsis in years:Survivors 52.5 (36–61.5)Non-survivors 54.5 (42.5–62.5) | Significantly elevated IL-10 levels in non-survivors compared to survivors | (59) |
| Adult | Post-operative sepsis: 35 - Survivors: 24 - Non-survivors: 11 Post-operative non-sepsis controls: 85 Mean time to mortality 22.3 (±6.6) days. Time from sepsis onset to death not described |
Blood sample was taken at time of initial suspicion of sepsisMean (±SEM) age at sepsis:61 (±2) years | Sepsis is associated with deficient IL-10 production. Sepsis survival correlated with recovery of pro-inflammatory secretion, but not IL-10 | (60) |
| Term(GA range 37–42 weeks) | Clinical (n = 10) and confirmed (n = 3) LOS: 13 - Sepsis: 4 - Severe sepsis: 6 - Septic shock: 3 |
Blood sample was taken at time of initial suspicion of sepsisMedian (IQR) age at sepsis: 10 (7–22) days | Increased IL-10 levels gradually increased are with sepsis severity, but not significantly | (53) |
| IL-10/TNFα RATIO | ||||
| Adult | Septic shock: 38 - Survivors: 22 - Non-survivors: 16 Mortality within 28 days after diagnosis. Time from sepsis onset to death not described |
Blood samples were taken on days 1–2, 3–4, 5–7, and 8–15 days following initial suspicion of sepsisMean age at sepsis:64 years (95% CI 59–69) | IL-10/TNFα ratio was significantly increased during the first days of sepsis in non-survivors compared to survivors | (52) |
| Adult | Infection (includes more than only sepsis): 399 - Survivors: 366 - Non-survivors: 33 Time from sepsis onset to death unclear |
Blood sample was taken when empirical antibiotics commencedMedian (IQR) age at sepsis: 61 (45–77) years | IL-10/TNFα ratio was significantly higher in non-survivors compared to survivors | (58) |
| Neonate of any GA | Not assessed | – | – | – |
GA, gestational age; LOS, late-onset sepsis; EOS, early-onset sepsis; VLBW, very low birth weight; SIRS, systemic inflammatory response syndrome; IL, interleukin; TNFα, tumour necrosis factor alpha; IFNγ, type II interferon; IQR, interquartile range; SD, standard deviation; CI, confidence interval.