南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (1): 6-22.doi: 10.12122/j.issn.1673-4254.2026.01.02
沙桐1(
), 王文研2(), 宣佳斌1(), 吴洁1, 石能贤1, 何劲1, 胡鸿彬1(), 张耀元1()
收稿日期:2025-03-05
接受日期:2025-07-13
出版日期:2026-01-20
发布日期:2026-01-16
通讯作者:
胡鸿彬,张耀元
E-mail:shatong_smu@163.com;wwy9438@gmail.com;798524682@qq.com;hobewoos@163.com;243204661@qq.com
作者简介:沙 桐，博士，医师，E-mail: shatong_smu@163.com
Tong SHA1(), Wenyan WANG2(), Jiabin XUAN1(), Jie WU1, Nengxian SHI1, Jin HE1, Hongbin HU1(), Yaoyuan ZHANG1()
Received:2025-03-05
Accepted:2025-07-13
Online:2026-01-20
Published:2026-01-16
Contact:
Hongbin HU, Yaoyuan ZHANG
E-mail:shatong_smu@163.com;wwy9438@gmail.com;798524682@qq.com;hobewoos@163.com;243204661@qq.com
About author:First author contact:aThese authors contributed equally to this work and should be deemed as co-first authors.Supported by:摘要：
目的 通过Th1/Th2细胞因子数据识别具有不同炎症特征的脓毒症亚型以制定个性化治疗方案，改善患者预后。 方法 在南方医科大学南方医院数据库中检索2020年6月1日~2022年2月1日期间接受Th1/Th2细胞因子检测的脓毒症患者数据。通过无监督K-均值聚类方法，根据Th1/Th2细胞因子水平对研究对象进行分类，主要研究终点为入ICU后7 d死亡率。采用Cox比例风险模型和限制平均生存时间（RMST）分析不同类型患者的生存结局。 结果 共纳入321例脓毒症患者。IL-6（HR=1.69，95% CI：1.22~2.34）和IL-10（HR=1.81，95% CI：1.37~2.40）被确定为患者入ICU后7 d内死亡率的独立预测因子。无监督K-均值聚类分析识别出3种炎症/免疫亚组：亚组1（n=166，低炎症反应）、亚组2（n=99，中度炎症反应伴免疫抑制）、亚组3（n=56，强烈炎症和免疫抑制）。与亚组1相比，亚组2和亚组3的患者入ICU后7 d内死亡风险更高（14.4% vs 23.2%，HR=4.30，95% CI：1.51~12.26； 14.4% vs 35.7%， HR=7.32， 95% CI：2.57~20.79）。 结论 处于保护性免疫反应状态（亚组1）的脓毒症患者短期预后较好，提示准确识别患者的炎症/免疫状态对精准治疗和改善结局的重要性。
沙桐, 王文研, 宣佳斌, 吴洁, 石能贤, 何劲, 胡鸿彬, 张耀元. 基于Th1/Th2细胞因子检测的脓毒症免疫状态分型及预后分析：一项回顾性研究[J]. 南方医科大学学报, 2026, 46(1): 6-22.
Tong SHA, Wenyan WANG, Jiabin XUAN, Jie WU, Nengxian SHI, Jin HE, Hongbin HU, Yaoyuan ZHANG. Identification of immune status subtypes and prognostic analysis of septic patients based on Th1/Th2 cytokine assays[J]. Journal of Southern Medical University, 2026, 46(1): 6-22.
Fig.1 Flow sheet of patient inclusion, data processing and subgroup identification. OPTICS: Ordering points to identify the clustering structure; SC: Silhouette score; DBI: Davies-Bouldin index; CH: Calinski-Harabasz score; t-SNE: t-distributed Stochastic Neighbor Embedding.
| Characteristics | Median [IQR]) or n(%) |
|---|---|
| Age (year) | 58.0 [46.0, 69.0] |
| Male | 242 (75.4%) |
| Admission type (surgery) | 164 (51.1%) |
| SOFA score | 7.0 [4.0, 10.0] |
| APACHE II score | 19.0 [13.0, 26.0] |
| Hypertension | 96 (29.9%) |
| Diabetes mellitus | 72 (22.4%) |
| Congestive heart failure | 36 (11.2%) |
| COPD | 14 (4.4%) |
| CKD | 29 (9.0%) |
| Chronic liver insufficiency | 59 (18.4%) |
| Malignant tumors | 99 (30.8%) |
| Immune system disorders | 29 (9.0%) |
| Trauma | 33 (10.3%) |
| ARDS | 113 (35.2%) |
| Antibiotics | 273 (85.0%) |
| Vasopressors | 213 (66.4%) |
| Norepinephrine equivalent | 0.09 [0.00, 0.24] |
| Positive inotropic drugs | 27 (8.4%) |
| Glucocorticoid | 32 (10.0%) |
| Ventilation time (h) | 3.0 [1.0, 9.0] |
| RRT | 91 (28.3%) |
| WBC (×109/L) | 12.09 [7.62, 16.65] |
| NEU (%) | 86.9 [79.9, 92.3] |
| LYM (%) | 6.8 [3.5, 11.5] |
| MONO (%) | 4.8 [2.8, 7.2] |
| PLT (×109/L) | 139.0 [70.0, 220.0] |
| CRP (mg/L) | 80.80 [37.77, 170.89] |
| PCT (ng/mL) | 2.23 [0.40, 11.18] |
| IL-2 (pg/mL) | 0.86 [0.55, 1.38] |
| IL-4 (pg/mL) | 1.13 [0.72, 1.69] |
| Log(IL-6) (pg/mL) | 5.01 [4.04, 6.63] |
| Log(IL-10) (pg/mL) | 2.53 [1.78, 3.55] |
| TNF (pg/mL) | 1.23 [0.87, 1.75] |
| IFN (pg/mL) | 1.32 [0.85, 1.90] |
| Hospital mortality at ICU 67 (20.9%) | |
Tab.1 Baseline characteristics of all participants in this study （n=321）
| Characteristics | Median [IQR]) or n(%) |
|---|---|
| Age (year) | 58.0 [46.0, 69.0] |
| Male | 242 (75.4%) |
| Admission type (surgery) | 164 (51.1%) |
| SOFA score | 7.0 [4.0, 10.0] |
| APACHE II score | 19.0 [13.0, 26.0] |
| Hypertension | 96 (29.9%) |
| Diabetes mellitus | 72 (22.4%) |
| Congestive heart failure | 36 (11.2%) |
| COPD | 14 (4.4%) |
| CKD | 29 (9.0%) |
| Chronic liver insufficiency | 59 (18.4%) |
| Malignant tumors | 99 (30.8%) |
| Immune system disorders | 29 (9.0%) |
| Trauma | 33 (10.3%) |
| ARDS | 113 (35.2%) |
| Antibiotics | 273 (85.0%) |
| Vasopressors | 213 (66.4%) |
| Norepinephrine equivalent | 0.09 [0.00, 0.24] |
| Positive inotropic drugs | 27 (8.4%) |
| Glucocorticoid | 32 (10.0%) |
| Ventilation time (h) | 3.0 [1.0, 9.0] |
| RRT | 91 (28.3%) |
| WBC (×109/L) | 12.09 [7.62, 16.65] |
| NEU (%) | 86.9 [79.9, 92.3] |
| LYM (%) | 6.8 [3.5, 11.5] |
| MONO (%) | 4.8 [2.8, 7.2] |
| PLT (×109/L) | 139.0 [70.0, 220.0] |
| CRP (mg/L) | 80.80 [37.77, 170.89] |
| PCT (ng/mL) | 2.23 [0.40, 11.18] |
| IL-2 (pg/mL) | 0.86 [0.55, 1.38] |
| IL-4 (pg/mL) | 1.13 [0.72, 1.69] |
| Log(IL-6) (pg/mL) | 5.01 [4.04, 6.63] |
| Log(IL-10) (pg/mL) | 2.53 [1.78, 3.55] |
| TNF (pg/mL) | 1.23 [0.87, 1.75] |
| IFN (pg/mL) | 1.32 [0.85, 1.90] |
| Hospital mortality at ICU 67 (20.9%) | |
Fig.2 Identification of the number of clusters of cytokine sub-phenotypes. A: Heat-map of pairwise correlations of the cytokines. B: OPTICS plot displaying a smooth rise in reachability distance. C: Heat map of the consensus matrix when the number of clusters was 3 (k=3). D: Histogram of SC, DBI, and CH values from k=2 to k=9 for clustering. E: Elbow plot showing the Total Within Cluster Sum of Squares (total WSS) for the number of clusters between 1 and 9. F: Visualization of K-means clustering results for 321 patients with sepsis based on cytokine profiles.
Fig.3 Results of consensus clustering. The CDF graph shows the consensus distribution of each cluster （A）. The delta area plot displays the relative change in the area under the CDF curve （B）. The maximum change in the area occurs between k=2 and k=9 when the relative increase in the area becomes significantly smaller. As shown in the CM heat map （C）, cluster 2 and cluster 3 identified by the K-means algorithm have clear boundaries, indicating good cluster stability in repeated iterations. The mean cluster consensus score was comparable between a scenario of 2 or 3 clusters （D）.
| Variable | 25th percentile | Median | Mean | 75th percentile |
|---|---|---|---|---|
| IL2 | 0.032 | 0.051 | 0.074 | 0.081 |
| IL4 | 0.118 | 0.185 | 0.203 | 0.277 |
| Log(IL-6) | 0.370 | 0.474 | 0.505 | 0.648 |
| Log(IL10) | 0.243 | 0.336 | 0.366 | 0.464 |
| TNF | 0.048 | 0.068 | 0.088 | 0.097 |
| IFN | 0.013 | 0.020 | 0.038 | 0.028 |
Tab.2 Distributions of the studied cytokines after Min-Max scaling
| Variable | 25th percentile | Median | Mean | 75th percentile |
|---|---|---|---|---|
| IL2 | 0.032 | 0.051 | 0.074 | 0.081 |
| IL4 | 0.118 | 0.185 | 0.203 | 0.277 |
| Log(IL-6) | 0.370 | 0.474 | 0.505 | 0.648 |
| Log(IL10) | 0.243 | 0.336 | 0.366 | 0.464 |
| TNF | 0.048 | 0.068 | 0.088 | 0.097 |
| IFN | 0.013 | 0.020 | 0.038 | 0.028 |
| Characteristics | Cluster 1 | Cluster 2 | Cluster 3 | P |
|---|---|---|---|---|
| n (%) | 166 (51.7%) | 99 (30.8%) | 56 (17.4%) | |
| Age (year) | 58.00 [45.25, 66.75] | 57.00 [45.50, 69.00] | 61.00 [50.00, 69.25] | 0.617 |
| Male | 125 (75.3) | 76 (76.8) | 41 (73.2) | 0.885 |
| Admission type (surgery) | 83 (50.0) | 55 (55.6) | 26 (46.4) | 0.508 |
| SOFA score | 6.00 [4.00, 8.00] | 8.00 [5.00, 11.00] | 11.00 [8.75, 12.00] | <0.001 |
| APACHE II score | 18.00 [12.00, 23.00] | 21.00 [14.00, 26.00] | 26.50 [19.75, 32.25] | <0.001 |
| Hypertension | 53 (31.9%) | 26 (26.3%) | 17 (30.4%) | 0.620 |
| Diabetes mellitus | 41 (24.7%) | 21 (21.2%) | 10 (17.9%) | 0.536 |
| Congestive heart failure | 21 (12.7%) | 8 (8.1%) | 7 (12.5%) | 0.493 |
| COPD | 8 (4.8%) | 4 (4.0%) | 2 (3.6%) | 0.909 |
| CKD | 16 (9.6%) | 9 (9.1%) | 4 (7.1%) | 0.853 |
| Chronic liver insufficiency | 32 (19.3%) | 15 (15.2%) | 12 (21.4%) | 0.570 |
| Malignant tumors | 50 (30.1%) | 32 (32.3%) | 17 (30.4%) | 0.928 |
| Immune system disorders | 16 (9.6%) | 10 (10.1%) | 3 (5.4%) | 0.568 |
| Trauma | 18 (10.8%) | 10 (10.1%) | 5 (8.9%) | 0.918 |
| ARDS | 45 (27.1%) | 38 (38.4%) | 30 (53.6%) | 0.001 |
| Antibiotics | 144 (86.7%) | 81 (81.8%) | 48 (85.7%) | 0.547 |
| Vasopressors | 86 (51.8%) | 75 (75.8%) | 52 (92.9%) | <0.001 |
| Norepinephrine equivalent | 0.03 [0.00, 0.16] | 0.10 [0.01, 0.24] | 0.22 [0.10, 0.60] | <0.001 |
| Positive inotropic drugs | 9 (5.4%) | 8 (8.1%) | 10 (17.9%) | 0.015 |
| Glucocorticoid | 13 (7.8%) | 8 (8.1%) | 11 (19.6%) | 0.029 |
| Ventilation time (h) | 3.00 [1.00, 8.75] | 3.00 [1.00, 8.00] | 6.00 [2.75, 10.00] | 0.018 |
| RRT | 33 (19.9%) | 30 (30.3%) | 28 (50.0%) | <0.001 |
| WBC (×109/L) | 11.29 [7.32, 15.16] | 12.81 [8.68, 17.00] | 14.18 [6.12, 20.75] | 0.086 |
| NEU (%) | 83.55 [78.17, 89.77] | 90.20 [84.15, 93.65] | 90.80 [84.42, 93.93] | <0.001 |
| LYM (%) | 8.60 [4.70, 13.17] | 4.90 [2.65, 9.30] | 4.55 [3.15, 8.43] | <0.001 |
| MONO (%) | 5.40 [3.52, 8.10] | 4.40 [2.65, 6.40] | 3.50 [1.60, 4.80] | <0.001 |
| PLT (×109/L) | 160.50 [96.25, 241.25] | 126.00 [63.00, 203.00] | 83.00 [47.00, 150.50] | <0.001 |
| CRP (mg/L) | 67.66 [26.70, 134.38] | 90.88 [49.50, 182.36] | 134.39 [63.26, 228.79] | <0.001 |
| PCT (ng/mL) | 1.15 [0.24, 4.20] | 3.07 [0.52, 9.09] | 23.38 [6.10, 68.22] | <0.001 |
| IL-2 (pg/mL) | 0.86 [0.52, 1.34] | 0.77 [0.52, 1.25] | 1.02 [0.67, 1.95] | 0.027 |
| IL-4 (pg/mL) | 1.14 [0.75, 1.76] | 0.96 [0.62, 1.41] | 1.46 [1.07, 1.94] | 0.003 |
| Log (IL-6, pg/mL) | 4.37 [3.46, 5.11] | 5.44 [4.59, 6.30] | 7.82 [7.10, 8.89] | <0.001 |
| Log (IL-10, pg/mL) | 1.81 [1.43, 2.19] | 3.17 [2.82, 3.62] | 4.86 [4.02, 5.41] | <0.001 |
| TNF (pg/mL) | 1.23 [0.85, 1.78] | 1.12 [0.90, 1.51] | 1.40 [0.95, 2.41] | 0.021 |
| IFN (pg/mL) | 1.27 [0.89, 1.89] | 1.18 [0.69, 1.67] | 1.62 [1.11, 2.27] | 0.005 |
Tab.3 Baseline characteristics of 321 patients stratified by the 3 clusters of cytokines mixture
| Characteristics | Cluster 1 | Cluster 2 | Cluster 3 | P |
|---|---|---|---|---|
| n (%) | 166 (51.7%) | 99 (30.8%) | 56 (17.4%) | |
| Age (year) | 58.00 [45.25, 66.75] | 57.00 [45.50, 69.00] | 61.00 [50.00, 69.25] | 0.617 |
| Male | 125 (75.3) | 76 (76.8) | 41 (73.2) | 0.885 |
| Admission type (surgery) | 83 (50.0) | 55 (55.6) | 26 (46.4) | 0.508 |
| SOFA score | 6.00 [4.00, 8.00] | 8.00 [5.00, 11.00] | 11.00 [8.75, 12.00] | <0.001 |
| APACHE II score | 18.00 [12.00, 23.00] | 21.00 [14.00, 26.00] | 26.50 [19.75, 32.25] | <0.001 |
| Hypertension | 53 (31.9%) | 26 (26.3%) | 17 (30.4%) | 0.620 |
| Diabetes mellitus | 41 (24.7%) | 21 (21.2%) | 10 (17.9%) | 0.536 |
| Congestive heart failure | 21 (12.7%) | 8 (8.1%) | 7 (12.5%) | 0.493 |
| COPD | 8 (4.8%) | 4 (4.0%) | 2 (3.6%) | 0.909 |
| CKD | 16 (9.6%) | 9 (9.1%) | 4 (7.1%) | 0.853 |
| Chronic liver insufficiency | 32 (19.3%) | 15 (15.2%) | 12 (21.4%) | 0.570 |
| Malignant tumors | 50 (30.1%) | 32 (32.3%) | 17 (30.4%) | 0.928 |
| Immune system disorders | 16 (9.6%) | 10 (10.1%) | 3 (5.4%) | 0.568 |
| Trauma | 18 (10.8%) | 10 (10.1%) | 5 (8.9%) | 0.918 |
| ARDS | 45 (27.1%) | 38 (38.4%) | 30 (53.6%) | 0.001 |
| Antibiotics | 144 (86.7%) | 81 (81.8%) | 48 (85.7%) | 0.547 |
| Vasopressors | 86 (51.8%) | 75 (75.8%) | 52 (92.9%) | <0.001 |
| Norepinephrine equivalent | 0.03 [0.00, 0.16] | 0.10 [0.01, 0.24] | 0.22 [0.10, 0.60] | <0.001 |
| Positive inotropic drugs | 9 (5.4%) | 8 (8.1%) | 10 (17.9%) | 0.015 |
| Glucocorticoid | 13 (7.8%) | 8 (8.1%) | 11 (19.6%) | 0.029 |
| Ventilation time (h) | 3.00 [1.00, 8.75] | 3.00 [1.00, 8.00] | 6.00 [2.75, 10.00] | 0.018 |
| RRT | 33 (19.9%) | 30 (30.3%) | 28 (50.0%) | <0.001 |
| WBC (×109/L) | 11.29 [7.32, 15.16] | 12.81 [8.68, 17.00] | 14.18 [6.12, 20.75] | 0.086 |
| NEU (%) | 83.55 [78.17, 89.77] | 90.20 [84.15, 93.65] | 90.80 [84.42, 93.93] | <0.001 |
| LYM (%) | 8.60 [4.70, 13.17] | 4.90 [2.65, 9.30] | 4.55 [3.15, 8.43] | <0.001 |
| MONO (%) | 5.40 [3.52, 8.10] | 4.40 [2.65, 6.40] | 3.50 [1.60, 4.80] | <0.001 |
| PLT (×109/L) | 160.50 [96.25, 241.25] | 126.00 [63.00, 203.00] | 83.00 [47.00, 150.50] | <0.001 |
| CRP (mg/L) | 67.66 [26.70, 134.38] | 90.88 [49.50, 182.36] | 134.39 [63.26, 228.79] | <0.001 |
| PCT (ng/mL) | 1.15 [0.24, 4.20] | 3.07 [0.52, 9.09] | 23.38 [6.10, 68.22] | <0.001 |
| IL-2 (pg/mL) | 0.86 [0.52, 1.34] | 0.77 [0.52, 1.25] | 1.02 [0.67, 1.95] | 0.027 |
| IL-4 (pg/mL) | 1.14 [0.75, 1.76] | 0.96 [0.62, 1.41] | 1.46 [1.07, 1.94] | 0.003 |
| Log (IL-6, pg/mL) | 4.37 [3.46, 5.11] | 5.44 [4.59, 6.30] | 7.82 [7.10, 8.89] | <0.001 |
| Log (IL-10, pg/mL) | 1.81 [1.43, 2.19] | 3.17 [2.82, 3.62] | 4.86 [4.02, 5.41] | <0.001 |
| TNF (pg/mL) | 1.23 [0.85, 1.78] | 1.12 [0.90, 1.51] | 1.40 [0.95, 2.41] | 0.021 |
| IFN (pg/mL) | 1.27 [0.89, 1.89] | 1.18 [0.69, 1.67] | 1.62 [1.11, 2.27] | 0.005 |
Fig.4 Clinical features of the 3 inflammatory subtypes of sepsis. A: Violin plots of serum cytokine levels in 3 inflammatory subtypes of sepsis. The X-axis represents the 3 subtypes, and the Y-axis represents serum cytokine levels. Comparisons between groups were corrected by false discovery rate (FDR). B: Box plots of mSOFA scores, APACHE-II scores, CRP levels, and PCT levels in the 3 inflammatory subtypes. C: Radar plots of the distribution of comorbidities and treatments in the 3 inflammatory subtypes (DM: Diabetes mellitus; CHF: Congestive heart failure; COPD: Chronic obstructive pulmonary disease; CKD: Chronic kidney disease; CLI: Chronic liver insufficiency; ISD: Immune system disorders; ARDS: Acute respiratory distress syndrome; RRT: Renal replacement therapy). D: Distribution of survival in the 3 inflammatory subtypes. ****P<0.0001.
Fig.5 Serum cytokine levels and risk of mortality in septic patients. A: Exposure-response relationship between circulating levels of each of the studied cytokines and the risk for 7 days mortality. The Y-axis represents the hazard ratio of the risk of death for a given value of circulating cytokine levels compared to the corresponding reference value (some values are converted to log10 on the Y-axis). The red dashed line indicates the 95% confidence interval, and the yellow dashed line the proportion of patients. B: Association between different serum cytokine levels and the risk of mortality within 7 days after ICU admission. Model 1 was adjusted for baseline age, sex, and admission type. Model 2 was additionally adjusted for SOFA score, APACHE II score, and relevant treatment history (use of antibiotics, vasopressors, norepinephrine equivalent, positive inotropic drugs, glucocorticoid, ventilation time, and RRT). Model 3 was further adjusted for history of chronic diseases (hypertension, diabetes, congestive heart failure, COPD, CKD, chronic liver insufficiency, malignant tumors, immune system disorders, trauma, ARDS, and CVD).
| Cytokines | 7-day mortality risk | 14-day mortality risk | 28-day mortality risk | |||||
|---|---|---|---|---|---|---|---|---|
| Overall | Non-linear | Overall | Non-linear | Overall | Non-linear | |||
| IL-2 | 0.478 | 0.230 | 0.566 | 0.287 | 0.319 | 0.164 | ||
| IL-4 | 0.695 | 0.475 | 0.867 | 0.757 | 0.912 | 0.847 | ||
| Log(IL-6) | 0.010 | 0.012 | 0.003 | 0.015 | 0.007 | 0.010 | ||
| Log(IL-10) | 0.001 | 0.238 | <0.001 | 0.061 | 0.013 | 0.165 | ||
| TNF | 0.038 | 0.012 | 0.074 | 0.023 | 0.064 | 0.022 | ||
| IFN | 0.345 | 0.148 | 0.669 | 0.417 | 0.719 | 0.491 | ||
Tab.4 P-values of overall and non-linear dose-response relationships of the 6 cytokines with mortality risk
| Cytokines | 7-day mortality risk | 14-day mortality risk | 28-day mortality risk | |||||
|---|---|---|---|---|---|---|---|---|
| Overall | Non-linear | Overall | Non-linear | Overall | Non-linear | |||
| IL-2 | 0.478 | 0.230 | 0.566 | 0.287 | 0.319 | 0.164 | ||
| IL-4 | 0.695 | 0.475 | 0.867 | 0.757 | 0.912 | 0.847 | ||
| Log(IL-6) | 0.010 | 0.012 | 0.003 | 0.015 | 0.007 | 0.010 | ||
| Log(IL-10) | 0.001 | 0.238 | <0.001 | 0.061 | 0.013 | 0.165 | ||
| TNF | 0.038 | 0.012 | 0.074 | 0.023 | 0.064 | 0.022 | ||
| IFN | 0.345 | 0.148 | 0.669 | 0.417 | 0.719 | 0.491 | ||
Fig.6 Exposure-response relationship between circulating levels of each of the studied cytokines and the risks of 14 day (A) and 28 day (B) mortality. The Y-axis represents the hazard ratios of mortality risk given the value of circulating cytokine levels compared to the corresponding reference value. The shaded areas indicate the 95 percent confidence intervals.
Fig.7 Association between different serum cytokine levels and risk of death at 14 days and 28 days after ICU admission.
| Variable | Crude model | Model l | Model 2 | Model 3 |
|---|---|---|---|---|
| 7-day mortality risk | ||||
| IL-2 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.51 (0.13, 1.95) | 0.32 (0.08, 1.29) | 0.19 (0.04, 0.96) | 0.18 (0.03, 1.17) |
| Q3 | 1.97 (0.77, 4.99) | 1.44 (0.55, 3.76) | 1.16 (0.36, 3.74) | 0.87 (0.23, 3.23) |
| Q4 | 1.12 (0.39, 3.21) | 0.61 (0.20, 1.90) | 0.35 (0.08, 1.48) | 0.09 (0.01, 0.65) |
| IL-4 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.40 (0.11, 1.52) | 0.39 (0.10, 1.48) | 0.29 (0.05, 1.60) | 0.25 (0.04, 1.79) |
| Q3 | 1.21 (0.47, 3.14) | 1.32 (0.50, 3.52) | 1.25 (0.40, 3.95) | 2.06 (0.50, 8.48) |
| Q4 | 1.17 (0.45, 3.04) | 0.79 (0.30, 2.12) | 0.57 (0.18, 1.81) | 0.38 (0.09, 1.62) |
| Log (IL-6) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 3.09 (0.60, 15.91) | 1.26 (0.23, 7.00) | 1.31 (0.12, 14.46) | 0.95 (0.04, 22.86) |
| Q3 | 4.32 (1.37, 13.62) | 3.66 (1.11, 12.04) | 3.88 (0.94, 15.97) | 3.92 (0.86, 17.82) |
| Q4 | 5.93 (2.16, 16.32) | 3.10 (0.99, 9.70) | 4.12 (1.02, 16.69) | 4.18 (0.90, 19.34) |
| Log (IL-10) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.79 (0.18, 3.55) | 0.78 (0.17, 3.67) | 0.67 (0.11, 4.07) | 0.34 (0.04, 3.03) |
| Q3 | 1.85 (0.54, 6.32) | 1.00 (0.27, 3.70) | 1.37 (0.29, 6.44) | 0.67 (0.11, 4.23) |
| Q4 | 4.32 (1.43, 13.01) | 2.02 (0.58, 7.06) | 2.10 (0.44, 10.10) | 0.79 (0.12, 5.13) |
| TNF | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 3.73 (0.79, 17.55) | 4.90 (1.00, 24.13) | 23.56 (1.64, 338.28) | 93.35 (4.62, 1885.71) |
| Q3 | 7.34 (1.67, 32.32) | 5.89 (1.30, 26.74) | 13.27 (1.12, 156.44) | 16.65 (1.23, 225.81) |
| Q4 | 2.52 (0.49, 13.01) | 2.31 (0.43, 12.55) | 2.44 (0.17, 35.54) | 1.01 (0.04, 23.51) |
| IFN | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.17 (0.36, 3.85) | 0.93 (0.28, 3.14) | 1.16 (0.30, 4.55) | 2.47 (0.46, 13.41) |
| Q3 | 2.05 (0.7, 5.99) | 1.54 (0.51, 4.67) | 1.53 (0.42, 5.62) | 3.22 (0.63, 16.49) |
| Q4 | 1.45 (0.48, 4.44) | 1.12 (0.35, 3.56) | 0.34 (0.08, 1.44) | 0.34 (0.06, 2.03) |
| 14-day mortality risk | ||||
| IL-2 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.89 (0.36, 2.22) | 0.56 (0.22, 1.43) | 0.47 (0.16, 1.37) | 0.45 (0.14, 1.46) |
| Q3 | 1.55 (0.71, 3.43) | 1.13 (0.50, 2.53) | 0.85 (0.32, 2.20) | 0.81 (0.30, 2.23) |
| Q4 | 0.92 (0.38, 2.21) | 0.50 (0.20, 1.29) | 0.33 (0.11, 1.02) | 0.28 (0.08, 0.95) |
| IL-4 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.62 (0.24, 1.57) | 0.59 (0.23, 1.52) | 0.57 (0.20, 1.64) | 0.53 (0.17, 1.69) |
| Q3 | 0.84 (0.36, 1.96) | 0.84 (0.36, 1.97) | 1.02 (0.41, 2.56) | 1.10 (0.42, 2.91) |
| Q4 | 1.11 (0.51, 2.43) | 0.74 (0.33, 1.67) | 0.69 (0.27, 1.76) | 0.59 (0.2,0 1.75) |
| Log (IL-6) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 4.20 (1.26, 13.98) | 1.84 (0.51, 6.60) | 1.51 (0.33, 6.92) | 1.43 (0.26, 7.85) |
| Q3 | 4.48 (1.80, 11.16) | 3.97 (1.55, 10.15) | 4.06 (1.45, 11.35) | 4.97 (1.62, 15.27) |
| Q4 | 4.64 (2.03, 10.60) | 2.65 (1.03, 6.83) | 2.44 (0.84, 7.06) | 2.64 (0.85, 8.17) |
| Log (IL-10) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
Tab.5 Crude and multi-variate adjusted hazard ratios （95% CI） of mortality risks in relation to levels of the 6 studied cytokines
| Variable | Crude model | Model l | Model 2 | Model 3 |
|---|---|---|---|---|
| 7-day mortality risk | ||||
| IL-2 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.51 (0.13, 1.95) | 0.32 (0.08, 1.29) | 0.19 (0.04, 0.96) | 0.18 (0.03, 1.17) |
| Q3 | 1.97 (0.77, 4.99) | 1.44 (0.55, 3.76) | 1.16 (0.36, 3.74) | 0.87 (0.23, 3.23) |
| Q4 | 1.12 (0.39, 3.21) | 0.61 (0.20, 1.90) | 0.35 (0.08, 1.48) | 0.09 (0.01, 0.65) |
| IL-4 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.40 (0.11, 1.52) | 0.39 (0.10, 1.48) | 0.29 (0.05, 1.60) | 0.25 (0.04, 1.79) |
| Q3 | 1.21 (0.47, 3.14) | 1.32 (0.50, 3.52) | 1.25 (0.40, 3.95) | 2.06 (0.50, 8.48) |
| Q4 | 1.17 (0.45, 3.04) | 0.79 (0.30, 2.12) | 0.57 (0.18, 1.81) | 0.38 (0.09, 1.62) |
| Log (IL-6) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 3.09 (0.60, 15.91) | 1.26 (0.23, 7.00) | 1.31 (0.12, 14.46) | 0.95 (0.04, 22.86) |
| Q3 | 4.32 (1.37, 13.62) | 3.66 (1.11, 12.04) | 3.88 (0.94, 15.97) | 3.92 (0.86, 17.82) |
| Q4 | 5.93 (2.16, 16.32) | 3.10 (0.99, 9.70) | 4.12 (1.02, 16.69) | 4.18 (0.90, 19.34) |
| Log (IL-10) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.79 (0.18, 3.55) | 0.78 (0.17, 3.67) | 0.67 (0.11, 4.07) | 0.34 (0.04, 3.03) |
| Q3 | 1.85 (0.54, 6.32) | 1.00 (0.27, 3.70) | 1.37 (0.29, 6.44) | 0.67 (0.11, 4.23) |
| Q4 | 4.32 (1.43, 13.01) | 2.02 (0.58, 7.06) | 2.10 (0.44, 10.10) | 0.79 (0.12, 5.13) |
| TNF | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 3.73 (0.79, 17.55) | 4.90 (1.00, 24.13) | 23.56 (1.64, 338.28) | 93.35 (4.62, 1885.71) |
| Q3 | 7.34 (1.67, 32.32) | 5.89 (1.30, 26.74) | 13.27 (1.12, 156.44) | 16.65 (1.23, 225.81) |
| Q4 | 2.52 (0.49, 13.01) | 2.31 (0.43, 12.55) | 2.44 (0.17, 35.54) | 1.01 (0.04, 23.51) |
| IFN | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.17 (0.36, 3.85) | 0.93 (0.28, 3.14) | 1.16 (0.30, 4.55) | 2.47 (0.46, 13.41) |
| Q3 | 2.05 (0.7, 5.99) | 1.54 (0.51, 4.67) | 1.53 (0.42, 5.62) | 3.22 (0.63, 16.49) |
| Q4 | 1.45 (0.48, 4.44) | 1.12 (0.35, 3.56) | 0.34 (0.08, 1.44) | 0.34 (0.06, 2.03) |
| 14-day mortality risk | ||||
| IL-2 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.89 (0.36, 2.22) | 0.56 (0.22, 1.43) | 0.47 (0.16, 1.37) | 0.45 (0.14, 1.46) |
| Q3 | 1.55 (0.71, 3.43) | 1.13 (0.50, 2.53) | 0.85 (0.32, 2.20) | 0.81 (0.30, 2.23) |
| Q4 | 0.92 (0.38, 2.21) | 0.50 (0.20, 1.29) | 0.33 (0.11, 1.02) | 0.28 (0.08, 0.95) |
| IL-4 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.62 (0.24, 1.57) | 0.59 (0.23, 1.52) | 0.57 (0.20, 1.64) | 0.53 (0.17, 1.69) |
| Q3 | 0.84 (0.36, 1.96) | 0.84 (0.36, 1.97) | 1.02 (0.41, 2.56) | 1.10 (0.42, 2.91) |
| Q4 | 1.11 (0.51, 2.43) | 0.74 (0.33, 1.67) | 0.69 (0.27, 1.76) | 0.59 (0.2,0 1.75) |
| Log (IL-6) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 4.20 (1.26, 13.98) | 1.84 (0.51, 6.60) | 1.51 (0.33, 6.92) | 1.43 (0.26, 7.85) |
| Q3 | 4.48 (1.80, 11.16) | 3.97 (1.55, 10.15) | 4.06 (1.45, 11.35) | 4.97 (1.62, 15.27) |
| Q4 | 4.64 (2.03, 10.60) | 2.65 (1.03, 6.83) | 2.44 (0.84, 7.06) | 2.64 (0.85, 8.17) |
| Log (IL-10) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Variables | Crude model | Model l | Model 2 | Model 3 |
|---|---|---|---|---|
| 7-days mortality risk | ||||
| IL2 | 1.02 (0.71, 1.46) | 0.92 (0.55, 1.53) | 0.95 (0.45, 2.00) | 0.36 (0.12, 1.11) |
| IL4 | 1.09 (0.77, 1.56) | 1.02 (0.71, 1.48) | 0.85 (0.56, 1.30) | 0.75 (0.47, 1.22) |
| Log-IL6 | 1.69 (1.22, 2.34) | 1.42 (0.97, 2.08) | 1.91 (1.08, 3.37) | 2.00 (1.03, 3.91) |
| Log-IL10 | 1.81 (1.37, 2.40) | 1.41 (1.00, 1.99) | 1.45 (0.90, 2.33) | 1.20 (0.70, 2.06) |
| TNF | 0.94 (0.57, 1.56) | 0.83 (0.45, 1.55) | 0.47 (0.20, 1.09) | 0.34 (0.13, 0.92) |
| IFN | 0.87 (0.50, 1.53) | 0.74 (0.41, 1.35) | 0.56 (0.21, 1.49) | 0.09 (0.01, 0.63) |
| 14-day mortality risk | ||||
| IL2 | 0.95 (0.66, 1.38) | 0.79 (0.46, 1.34) | 0.63 (0.31, 1.25) | 0.46 (0.20, 1.03) |
| IL4 | 1.06 (0.79, 1.44) | 1.00 (0.72, 1.38) | 0.98 (0.71, 1.36) | 0.99 (0.70, 1.41) |
| Log-IL6 | 1.62 (1.24, 2.12) | 1.39 (1.01, 1.91) | 1.37 (0.92, 2.04) | 1.45 (0.94, 2.22) |
| Log-IL10 | 1.71 (1.36, 2.15) | 1.30 (0.97, 1.73) | 1.40 (0.93, 2.10) | 1.35 (0.89, 2.05) |
| TNF | 0.79 (0.46, 1.37) | 0.61 (0.33, 1.12) | 0.35 (0.16, 0.77) | 0.30 (0.13, 0.71) |
| IFN | 0.91 (0.61, 1.37) | 0.75 (0.49, 1.16) | 0.57 (0.31, 1.03) | 0.41 (0.20, 0.84) |
| 28-day mortality risk | ||||
| IL2 | 1.08 (0.84, 1.39) | 1.02 (0.74, 1.39) | 0.97 (0.68, 1.38) | 1.00 (0.66, 1.53) |
| IL4 | 1.05 (0.81, 1.37) | 0.98 (0.74, 1.30) | 0.97 (0.73, 1.28) | 1.01 (0.75, 1.36) |
| Log-IL6 | 1.36 (1.08, 1.72) | 1.16 (0.89, 1.51) | 1.26 (0.90, 1.76) | 1.38 (0.98, 1.96) |
| Log-IL10 | 1.37 (1.11, 1.69) | 1.07 (0.83, 1.38) | 1.34 (0.93, 1.95) | 1.32 (0.91, 1.92) |
| TNF | 0.73 (0.44, 1.20) | 0.56 (0.32, 0.98) | 0.43 (0.23, 0.82) | 0.45 (0.23, 0.86) |
| IFN | 0.91 (0.62, 1.33) | 0.81 (0.54, 1.20) | 0.69 (0.42, 1.13) | 0.57 (0.33, 0.98) |
Tab.6 Crude and multi-variate adjusted hazard ratios （95% CIs） of the 7-， 14-， and 28-day mortality risks in relation to the per SD increase in the six studied cytokines
| Variables | Crude model | Model l | Model 2 | Model 3 |
|---|---|---|---|---|
| 7-days mortality risk | ||||
| IL2 | 1.02 (0.71, 1.46) | 0.92 (0.55, 1.53) | 0.95 (0.45, 2.00) | 0.36 (0.12, 1.11) |
| IL4 | 1.09 (0.77, 1.56) | 1.02 (0.71, 1.48) | 0.85 (0.56, 1.30) | 0.75 (0.47, 1.22) |
| Log-IL6 | 1.69 (1.22, 2.34) | 1.42 (0.97, 2.08) | 1.91 (1.08, 3.37) | 2.00 (1.03, 3.91) |
| Log-IL10 | 1.81 (1.37, 2.40) | 1.41 (1.00, 1.99) | 1.45 (0.90, 2.33) | 1.20 (0.70, 2.06) |
| TNF | 0.94 (0.57, 1.56) | 0.83 (0.45, 1.55) | 0.47 (0.20, 1.09) | 0.34 (0.13, 0.92) |
| IFN | 0.87 (0.50, 1.53) | 0.74 (0.41, 1.35) | 0.56 (0.21, 1.49) | 0.09 (0.01, 0.63) |
| 14-day mortality risk | ||||
| IL2 | 0.95 (0.66, 1.38) | 0.79 (0.46, 1.34) | 0.63 (0.31, 1.25) | 0.46 (0.20, 1.03) |
| IL4 | 1.06 (0.79, 1.44) | 1.00 (0.72, 1.38) | 0.98 (0.71, 1.36) | 0.99 (0.70, 1.41) |
| Log-IL6 | 1.62 (1.24, 2.12) | 1.39 (1.01, 1.91) | 1.37 (0.92, 2.04) | 1.45 (0.94, 2.22) |
| Log-IL10 | 1.71 (1.36, 2.15) | 1.30 (0.97, 1.73) | 1.40 (0.93, 2.10) | 1.35 (0.89, 2.05) |
| TNF | 0.79 (0.46, 1.37) | 0.61 (0.33, 1.12) | 0.35 (0.16, 0.77) | 0.30 (0.13, 0.71) |
| IFN | 0.91 (0.61, 1.37) | 0.75 (0.49, 1.16) | 0.57 (0.31, 1.03) | 0.41 (0.20, 0.84) |
| 28-day mortality risk | ||||
| IL2 | 1.08 (0.84, 1.39) | 1.02 (0.74, 1.39) | 0.97 (0.68, 1.38) | 1.00 (0.66, 1.53) |
| IL4 | 1.05 (0.81, 1.37) | 0.98 (0.74, 1.30) | 0.97 (0.73, 1.28) | 1.01 (0.75, 1.36) |
| Log-IL6 | 1.36 (1.08, 1.72) | 1.16 (0.89, 1.51) | 1.26 (0.90, 1.76) | 1.38 (0.98, 1.96) |
| Log-IL10 | 1.37 (1.11, 1.69) | 1.07 (0.83, 1.38) | 1.34 (0.93, 1.95) | 1.32 (0.91, 1.92) |
| TNF | 0.73 (0.44, 1.20) | 0.56 (0.32, 0.98) | 0.43 (0.23, 0.82) | 0.45 (0.23, 0.86) |
| IFN | 0.91 (0.62, 1.33) | 0.81 (0.54, 1.20) | 0.69 (0.42, 1.13) | 0.57 (0.33, 0.98) |
| Variable | Crude model | Model l | Model 2 | Model 3 |
|---|---|---|---|---|
| Q2 | 1.29 (0.39, 4.23) | 1.24 (0.36, 4.26) | 0.97 (0.25, 3.72) | 0.74 (0.17, 3.17) |
| Q3 | 2.07 (0.71, 6.06) | 1.27 (0.41, 3.94) | 0.97 (0.28, 3.35) | 0.86 (0.23, 3.19) |
| Q4 | 5.2 (1.96, 13.8) | 2.66 (0.87, 8.11) | 1.90 (0.55, 6.55) | 1.58 (0.43, 5.82) |
| TNF | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.93 (0.78, 4.79) | 2.62 (1.02, 6.76) | 4.72 (1.44, 15.43) | 6.48 (1.75, 23.98) |
| Q3 | 2.31 (0.94, 5.66) | 1.86 (0.74, 4.69) | 2.48 (0.83, 7.45) | 2.69 (0.80, 9.01) |
| Q4 | 0.83 (0.28, 2.48) | 0.64 (0.21, 1.98) | 0.45 (0.11, 1.84) | 0.45 (0.09, 2.18) |
| IFN | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.92 (0.36, 2.32) | 0.75 (0.29, 1.92) | 1.17 (0.41, 3.30) | 1.28 (0.44, 3.75) |
| Q3 | 1.36 (0.58, 3.18) | 1.07 (0.45, 2.57) | 0.77 (0.28, 2.12) | 0.98 (0.33, 2.85) |
| Q4 | 1.03 (0.43, 2.50) | 0.82 (0.33, 2.03) | 0.48 (0.17, 1.40) | 0.41 (0.13, 1.34) |
| 28-day mortality risk | ||||
| IL-2 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.27 (0.57, 2.84) | 0.86 (0.38, 1.97) | 0.63 (0.25, 1.60) | 0.59 (0.21, 1.65) |
| Q3 | 1.72 (0.82, 3.61) | 1.33 (0.62, 2.85) | 0.97 (0.41, 2.27) | 0.90 (0.36, 2.25) |
| Q4 | 1.37 (0.65, 2.89) | 0.85 (0.38, 1.88) | 0.60 (0.25, 1.46) | 0.61 (0.23, 1.59) |
| IL-4 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.71 (0.32, 1.57) | 0.69 (0.31, 1.53) | 0.64 (0.27, 1.53) | 0.74 (0.29, 1.89) |
| Q3 | 0.86 (0.41, 1.78) | 0.83 (0.40, 1.73) | 0.93 (0.42, 2.03) | 1.08 (0.47, 2.51) |
| Q4 | 1.21 (0.61, 2.40) | 0.83 (0.41, 1.69) | 0.77 (0.36, 1.66) | 0.86 (0.36, 2.05) |
| Log (IL-6) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 3.49 (1.34, 9.10) | 1.90 (0.67, 5.38) | 2.37 (0.76, 7.39) | 2.26 (0.65, 7.88) |
| Q3 | 3.34 (1.59, 7.02) | 3.00 (1.41, 6.38) | 3.40 (1.47, 7.82) | 4.91 (2.00, 12.03) |
| Q4 | 2.94 (1.51, 5.71) | 1.77 (0.84, 3.73) | 2.39 (1.00, 5.72) | 3.15 (1.23, 8.08) |
| Log (IL-10) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.48 (0.63, 3.47) | 1.43 (0.59, 3.49) | 1.13 (0.45, 2.86) | 1.12 (0.41, 3.03) |
| Q3 | 1.32 (0.56, 3.09) | 0.84 (0.34, 2.07) | 0.69 (0.26, 1.84) | 0.70 (0.26, 1.94) |
| Q4 | 2.84 (1.30, 6.17) | 1.59 (0.66, 3.83) | 1.89 (0.71, 5.01) | 1.83 (0.65, 5.10) |
| TNF | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.17 (0.55, 2.51) | 1.42 (0.65, 3.10) | 1.72 (0.68, 4.36) | 1.96 (0.71, 5.42) |
| Q3 | 1.87 (0.93, 3.79) | 1.48 (0.71, 3.06) | 2.09 (0.94, 4.66) | 2.74 (1.11, 6.76) |
| Q4 | 0.57 (0.23, 1.40) | 0.44 (0.18, 1.12) | 0.34 (0.11, 1.06) | 0.43 (0.13, 1.39) |
| IFN | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.03 (0.47, 2.28) | 0.92 (0.41, 2.07) | 1.17 (0.50, 2.76) | 1.49 (0.61, 3.66) |
| Q3 | 1.28 (0.60, 2.75) | 1.05 (0.49, 2.28) | 0.91 (0.39, 2.13) | 1.19 (0.46, 3.09) |
| Q4 | 1.02 (0.47, 2.24) | 0.96 (0.43, 2.14) | 0.86 (0.35, 2.12) | 0.88 (0.33, 2.34) |
Tab.5 (Continued)
| Variable | Crude model | Model l | Model 2 | Model 3 |
|---|---|---|---|---|
| Q2 | 1.29 (0.39, 4.23) | 1.24 (0.36, 4.26) | 0.97 (0.25, 3.72) | 0.74 (0.17, 3.17) |
| Q3 | 2.07 (0.71, 6.06) | 1.27 (0.41, 3.94) | 0.97 (0.28, 3.35) | 0.86 (0.23, 3.19) |
| Q4 | 5.2 (1.96, 13.8) | 2.66 (0.87, 8.11) | 1.90 (0.55, 6.55) | 1.58 (0.43, 5.82) |
| TNF | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.93 (0.78, 4.79) | 2.62 (1.02, 6.76) | 4.72 (1.44, 15.43) | 6.48 (1.75, 23.98) |
| Q3 | 2.31 (0.94, 5.66) | 1.86 (0.74, 4.69) | 2.48 (0.83, 7.45) | 2.69 (0.80, 9.01) |
| Q4 | 0.83 (0.28, 2.48) | 0.64 (0.21, 1.98) | 0.45 (0.11, 1.84) | 0.45 (0.09, 2.18) |
| IFN | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.92 (0.36, 2.32) | 0.75 (0.29, 1.92) | 1.17 (0.41, 3.30) | 1.28 (0.44, 3.75) |
| Q3 | 1.36 (0.58, 3.18) | 1.07 (0.45, 2.57) | 0.77 (0.28, 2.12) | 0.98 (0.33, 2.85) |
| Q4 | 1.03 (0.43, 2.50) | 0.82 (0.33, 2.03) | 0.48 (0.17, 1.40) | 0.41 (0.13, 1.34) |
| 28-day mortality risk | ||||
| IL-2 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.27 (0.57, 2.84) | 0.86 (0.38, 1.97) | 0.63 (0.25, 1.60) | 0.59 (0.21, 1.65) |
| Q3 | 1.72 (0.82, 3.61) | 1.33 (0.62, 2.85) | 0.97 (0.41, 2.27) | 0.90 (0.36, 2.25) |
| Q4 | 1.37 (0.65, 2.89) | 0.85 (0.38, 1.88) | 0.60 (0.25, 1.46) | 0.61 (0.23, 1.59) |
| IL-4 | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 0.71 (0.32, 1.57) | 0.69 (0.31, 1.53) | 0.64 (0.27, 1.53) | 0.74 (0.29, 1.89) |
| Q3 | 0.86 (0.41, 1.78) | 0.83 (0.40, 1.73) | 0.93 (0.42, 2.03) | 1.08 (0.47, 2.51) |
| Q4 | 1.21 (0.61, 2.40) | 0.83 (0.41, 1.69) | 0.77 (0.36, 1.66) | 0.86 (0.36, 2.05) |
| Log (IL-6) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 3.49 (1.34, 9.10) | 1.90 (0.67, 5.38) | 2.37 (0.76, 7.39) | 2.26 (0.65, 7.88) |
| Q3 | 3.34 (1.59, 7.02) | 3.00 (1.41, 6.38) | 3.40 (1.47, 7.82) | 4.91 (2.00, 12.03) |
| Q4 | 2.94 (1.51, 5.71) | 1.77 (0.84, 3.73) | 2.39 (1.00, 5.72) | 3.15 (1.23, 8.08) |
| Log (IL-10) | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.48 (0.63, 3.47) | 1.43 (0.59, 3.49) | 1.13 (0.45, 2.86) | 1.12 (0.41, 3.03) |
| Q3 | 1.32 (0.56, 3.09) | 0.84 (0.34, 2.07) | 0.69 (0.26, 1.84) | 0.70 (0.26, 1.94) |
| Q4 | 2.84 (1.30, 6.17) | 1.59 (0.66, 3.83) | 1.89 (0.71, 5.01) | 1.83 (0.65, 5.10) |
| TNF | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.17 (0.55, 2.51) | 1.42 (0.65, 3.10) | 1.72 (0.68, 4.36) | 1.96 (0.71, 5.42) |
| Q3 | 1.87 (0.93, 3.79) | 1.48 (0.71, 3.06) | 2.09 (0.94, 4.66) | 2.74 (1.11, 6.76) |
| Q4 | 0.57 (0.23, 1.40) | 0.44 (0.18, 1.12) | 0.34 (0.11, 1.06) | 0.43 (0.13, 1.39) |
| IFN | ||||
| Q1 | 1.00 | 1.00 | 1.00 | 1.00 |
| Q2 | 1.03 (0.47, 2.28) | 0.92 (0.41, 2.07) | 1.17 (0.50, 2.76) | 1.49 (0.61, 3.66) |
| Q3 | 1.28 (0.60, 2.75) | 1.05 (0.49, 2.28) | 0.91 (0.39, 2.13) | 1.19 (0.46, 3.09) |
| Q4 | 1.02 (0.47, 2.24) | 0.96 (0.43, 2.14) | 0.86 (0.35, 2.12) | 0.88 (0.33, 2.34) |
Fig.8 Association of cytokine inflammatory subtypes with ICU mortality risk. A: Risk score plot. B: Kaplan-Meier analysis of different cytokine inflammatory subtypes on days 7, 14, and 28 in septic patients in the ICU. C: Forest plots of 7-day, 14-day, and 28-day mortality risk for the 3 inflammatory subtypes. The difference in RMST (95% CI) was calculated using the difference in restricted mean survival time between the two groups (RMSTcluster2-RMSTcluster1, or RMSTcluster3-RMSTcluster1), implying a decrease in survival in the other clustes relative to Cluster 1.
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