Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and Mortality in Severe Septic Patients
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Design and Subjects
4.2. Variables Recorded
4.3. Blood Samples and Determinations
4.4. Statistical Methods
5. Conclusions
Author Contributions
Conflicts of Interest
Abbreviations
SOFA | Sepsis-related organ failure assessment |
COPD | Chronic obstructive pulmonary disease |
aPTT | Activated partial thromboplastin time |
IL | Interleukin |
INR | International normalized ratio |
PaO2 | Pressure of arterial oxygen |
FIO2 | Fraction inspired oxygen |
References
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Demographic and Clinical Characteristics | GG (n = 123) | GC (n = 110) | CC (n = 30) | p-Value |
---|---|---|---|---|
Bloodstream infection—n (%) | 17 (13.8) | 22 (20.0) | 3 (10.0) | 0.28 |
COPD—n (%) | 15 (12.2) | 14 (12.7) | 6 (20.0) | 0.52 |
Diabetes mellitus—n (%) | 39 (31.7) | 34 (30.9) | 6 (20.0) | 0.44 |
Empiric antimicrobial treatment—n (%) | – | – | – | 0.28 |
Unknown whether adequate due to negative cultures | 63 (51.2) | 52 (47.3) | 17 (56.7) | – |
Unknown whether adequate due to diagnosis by antigenuria | 5 (4.1) | 1 (0.9) | 1 (3.3) | – |
Adequate | 45 (36.6) | 52 (47.3) | 11 (36.7) | – |
Inadequate | 11 (8.9) | 4 (3.6) | 1 (3.3) | – |
Female gender—n (%) | 43 (35.0) | 35 (31.8) | 12 (40.0) | 0.69 |
Ischemic heart disease—n (%) | 16 (13.0) | 9 (8.2) | 4 (13.3) | 0.46 |
Mechanical ventilation—n (%) | 104 (84.6) | 95 (86.3) | 24 (80.0) | 0.51 |
Microorganism responsible—n (%) | – | – | – | – |
Unknown | 63 (51.2) | 52 (47.3) | 17 (56.7) | 0.63 |
Gram-positive | 28 (22.8) | 30 (27.3) | 7 (23.3) | 0.72 |
Gram-negative | 32 (26.0) | 27 (24.5) | 8 (26.7) | 0.96 |
Fungii | 6 (4.9) | 1 (0.9) | 0 | 0.11 |
Anaerobe | 1 (0.8) | 1 (0.9) | 0 | 0.88 |
Mortality at 30 days—n (%) | 47 (38.2) | 36 (32.7) | 3 (10.0) | 0.01 |
Septic shock—n (%) | 104 (84.6) | 95 (87.2) | 24 (80.0) | 0.60 |
Site of infection—n (%) | – | – | – | 0.84 |
Respiratory | 64 (52.0) | 67 (60.9) | 14 (46.7) | – |
Abdominal | 39 (31.7) | 28 (25.5) | 10 (33.3) | – |
Neurological | 4 (3.3) | 1 (0.9) | 0 | – |
Urinary | 6 (4.9) | 5 (4.5) | 2 (6.7) | – |
Skin | 5 (4.1) | 4 (3.6) | 2 (6.7) | – |
Endocarditis | 5 (4.1) | 4 (3.6) | 2 (6.7) | – |
Osteomyelitis | 0 | 1 (0.9) | 0 | – |
Age—median years (p25–75) | 56 (43–68) | 61 (50–70) | 63 (51–78) | 0.32 |
APACHE-II score—median (p25–75) | 20 (15–25) | 21 (16–25) | 20 (17–22) | 0.62 |
aPTT (seconds)—median (p25–75) | 35 (29–44) | 33 (28–43) | 28 (27–43) | 0.09 |
Bilirubin (mg/dl)—median (p25–75) | 0.90 (0.50–2.49) | 0.80 (0.41–1.50) | 0.80 (0.51–1.63) | 0.20 |
Creatinine (mg/dl)—median (p25–75) | 1.30 (0.70–2.28) | 1.40 (0.90–2.45) | 1.60 (0.90–2.55) | 0.94 |
Hospitalization before enrollment in the study (days)—median (p25–75) | 0 (0–5) | 0 (0–5) | 0 (0–3) | 0.20 |
GCS—median (p25–75) | 15 (13–15) | 15 (8–15) | 14 (10–15) | 0.40 |
Interleukin-6 levels (pg/mL)—median (p25-75) | 429 (74–1034) | 136 (41–852) | 21 (13–116) | <0.001 |
INR—median (p25–75) | 1.42 (1.20–1.71) | 1.20 (1.06–1.50) | 1.36 (1.11–1.50) | 0.0033 |
Lactic acid (mmol/L)—median (p25–75) | 2.15 (1.13–4.38) | 2.20 (1.25–4.45) | 2.00 (1.15–3.15) | 0.11 |
Leukocytes (cells/mm3)—median × 103 (p25–75) | 14.1 (8.9–20.1) | 15.2 (7.9–22.0) | 16.2 (13.4–22.4) | 0.57 |
Pa02/FI02 ratio—median (p25–75) | 194 (111–265) | 160 (102–221) | 250 (172–298) | 0.001 |
Platelets (cells/mm3)—median × 103 (p25–75) | 165 (90–243) | 179 (101–270) | 210 (93–267) | 0.17 |
SOFA score—median (p25−75) | 10 (7–13) | 10 (7–12) | 8 (6–11) | 0.02 |
Predictors | Odds Ratio | 95% Confidence Interval | p-Value |
---|---|---|---|
First Model | – | – | – |
SOFA (points) | 1.15 | 1.023–1.284 | 0.02 |
Lactic acid levels (mmol/L) | 1.23 | 1.063–1.430 | 0.006 |
Age (years) | 1.02 | 0.990–1.042 | 0.23 |
Genotype of interleukin-6 (CC vs. GG) | 0.21 | 0.053–0.838 | 0.03 |
Second Model | – | – | – |
SOFA (points) | 1.22 | 1.068–1.395 | 0.003 |
Lactic acid levels (mmol/L) | 1.08 | 0.933–1.254 | 0.30 |
Age (years) | 1.02 | 0.988–1.052 | 0.22 |
Genotype of interleukin-6 (CC vs. GC) | 0.28 | 0.074–1.037 | 0.057 |
Third Model | – | – | – |
SOFA (points) | 1.16 | 1.062–1.263 | 0.001 |
Lactic acid levels (mmol/L) | 1.14 | 1.029–1.033 | 0.01 |
Age (years) | 1.01 | 0.993–1.033 | 0.22 |
Serum interleukin-6 levels (pg/mL) | 1.001 | 1.0001–1.001 | 0.002 |
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Lorente, L.; Martín, M.M.; Pérez-Cejas, A.; Barrios, Y.; Solé-Violán, J.; Ferreres, J.; Labarta, L.; Díaz, C.; Jiménez, A. Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and Mortality in Severe Septic Patients. Int. J. Mol. Sci. 2016, 17, 1861. https://doi.org/10.3390/ijms17111861
Lorente L, Martín MM, Pérez-Cejas A, Barrios Y, Solé-Violán J, Ferreres J, Labarta L, Díaz C, Jiménez A. Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and Mortality in Severe Septic Patients. International Journal of Molecular Sciences. 2016; 17(11):1861. https://doi.org/10.3390/ijms17111861
Chicago/Turabian StyleLorente, Leonardo, María M. Martín, Antonia Pérez-Cejas, Ysamar Barrios, Jordi Solé-Violán, José Ferreres, Lorenzo Labarta, César Díaz, and Alejandro Jiménez. 2016. "Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and Mortality in Severe Septic Patients" International Journal of Molecular Sciences 17, no. 11: 1861. https://doi.org/10.3390/ijms17111861