2026 年 33 巻 2 号 p. 195-203
Aims: Interleukin-6 (IL-6) is a cytokine involved in the development of atherosclerosis and ischemic stroke. Herein, we investigated the association between serum IL-6 levels at stroke onset and long-term outcomes in patients with ischemic stroke.
Methods: This prospective observational study enrolled 655 consecutive patients (mean age, 70 years; male, 62.1%) with ischemic stroke within one week of onset followed-up for one year. Patients were divided into 3 groups according to baseline serum IL-6 tertiles: tertile 1, ＜2.6 pg/mL (n = 216); tertile 2, 2.6-6.1 pg/mL (n = 217); and tertile 3, ＞= 6.2 pg/mL (n = 222). We evaluated the association of serum IL-6 levels with a composite of major adverse cardiovascular events (MACE; nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death) and the poor functional outcome defined as modified Rankin Scale score of ≥ 3 at one year.
Results: Higher serum IL-6 levels were associated with increased prevalence of chronic kidney disease, atrial fibrillation, chronic heart disease, active cancer, and post-stroke pneumonia. The three groups showed significant differences in the one-year MACE risk (annual rate, 11.2%, 10.8%, and 19.1% in the tertiles 1, tertile 2, and tertile 3 groups, respectively). Higher serum IL-6 levels were significantly associated with poor functional outcomes at one year after stroke (14.4%, 29.5%, and 56.8% in the tertile 1, tertile 2, and tertile 3 groups, respectively; P＜0.001), even when adjusting for baseline covariates and MACE during follow-up.
Conclusions: Higher serum IL-6 level at ischemic stroke onset was an independent predictor of poor functional prognosis at one year.
Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and thus in the development of ischemic stroke1, 2). Moreover, previous studies have suggested that blood levels of pro-inflammatory cytokines early in the onset of stroke are positively correlated with stroke severity and poor prognosis in stroke patients3). Interleukin-6 (IL-6) is an upstream cytokine that plays a critical role in these processes4). Research has indicated that the higher serum levels of IL-6 are strong predictors of atherosclerotic cardiovascular events, including stroke5). Furthermore, IL-6 has received significant attention for its relevance in the functional prognosis and mortality after ischemic stroke6-9). However, there is a lack of data that comprehensively evaluated the association between IL-6 levels and long-term outcome. Given that long-term outcomes are affected by post-stroke cardiovascular events, this study sought to determine whether IL-6 levels independently predict 1-year outcomes, regardless of newly occurring cardiovascular events.
The Tokyo Women’s Medical University (TWMU) Stroke Registry is an ongoing, prospective, single-center, observational study that enrolled participants with acute ischemic stroke or transient ischemic attack (TIA) within one week of onset, who were hospitalized at our center. This study conformed to the ethical principles of the 1975 Declaration of Helsinki, the Ethical Guidelines for Epidemiological Research of the Japanese government, and the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. The study protocol was approved by the Ethics Committee of Tokyo Women’s Medical University Hospital (approval no. 2955-R2), and written informed consent was obtained from all patients. The TWMU Stroke Registry is registered at UMIN000031913 (https://upload.umin.ac.jp). The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Among the 1090 patients assessed for eligibility between November 2013 and June 2021, 23 were excluded because their final diagnosis was a stroke mimic, or they were admitted more than one week following stroke onset. A further 94 patients with transient ischemic attacks were excluded. In addition, we excluded a further 66 patients with a premorbid modified Rankin Scale (mRS) score ≥ 3, 236 who had no IL-6 data at baseline, and 16 who failed to undergo sufficient follow-up. Finally, 655 patients (mean age, 70.1 years; male, 62.1%) were included in the analysis (Fig.1).
Abbreviations: IL-6 = interleukin-6; TWMU = Tokyo Women’s Medical University.
All stroke cases were diagnosed based on neurological and radiological findings by board-certified stroke neurologists. Upon admission, neurological symptoms were assessed using the National Institutes of Health Stroke Scale (NIHSS) score. The following patient data were collected: demographic characteristics, clinical symptoms during the qualifying event, medical history, investigations (including standard blood chemistry, brain and cerebral artery imaging, carotid ultrasound, 24-hour Holter electrocardiogram, and ultrasonic echocardiography), management (medical treatment, revascularization procedure, and surgery), and the occurrence of clinical events after the qualifying event using a structured case report form. The etiologic subtypes of ischemic stroke were classified as atherothrombosis, cardioembolism, small vessel disease, other determined causes, and undetermined causes, in accordance with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification10).
Serum IL-6 LevelsSerum IL-6 levels were measured upon hospital admission using a chemiluminescent enzyme immunoassay (CLEIA), performed by SRL Inc. (Tokyo, Japan) according to the manufacturer’s standard protocol (reference range: ≤ 5.8 pg/mL). Patients were divided into three groups according to serum IL-6 level tertiles: (i) tertile 1, ＜2.6 pg/mL (n = 216); (ii) tertile 2, 2.6-6.1 pg/mL (n = 217); and (iii) tertile 3, ＞= 6.2 pg/mL (n = 222).
Follow up and OutcomesPatients underwent follow-up visits at discharge at three months, one year, and three years after enrollment. The one-year outcomes were reported in this study. At each visit, the treatment, occurrence of clinical events, and mRS scores were recorded. If the patient could not be followed-up, a relative or caregiver was interviewed via telephone. The primary outcome was a composite of major adverse cardiovascular events (MACE), including nonfatal stroke (either ischemic or hemorrhagic), nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. The secondary outcomes included stroke (ischemic or hemorrhagic), all-cause mortality, and poor functional prognosis, defined as a mRS score of ≥ 3 at one year.
Statistical AnalysisContinuous variables are presented as the mean (standard deviation) in cases of normal distribution or median (interquartile range). Qualitative variables are expressed as frequencies (percentages). Comparisons were made between multiple groups using one-way analysis of variance or the Mann–Whitney U test for quantitative variables, the χ2 test for categorical variables, and the log-rank test for censored variables. Event rates were estimated using the Kaplan-Meier method, and intergroup differences were assessed using the log-rank test. Cox proportional hazard regression models were applied to evaluate the association between serum IL-6 levels and the risk of recurrent vascular events by calculating hazard ratios (HRs) and 95% confidence intervals (CIs). Age, sex, variables with P＜0.10 in the univariate analysis (i.e., body mass index, diabetes mellitus, chronic kidney disease, atrial fibrillation, chronic heart failure, pneumonia, active cancer, initial NIHSS scores, and TOAST classification), and treatments with tissue plasminogen activator and mechanical thrombectomy were included in the multivariate adjustments. Data for patients with no information after one year were censored at the final available follow-up. For a given outcome, patients who died of causes other than the outcome were excluded at the time of death. To identify predictors of poor functional outcomes, we performed multiple logistic regression analysis, adjusting for age, sex, body mass index, diabetes mellitus, chronic kidney disease, atrial fibrillation, chronic heart failure, pneumonia, active cancer, initial NIHSS scores, TOAST classification, tissue plasminogen activator, mechanical thrombectomy, and occurrence of MACE. Odds ratios (ORs) and 95% CIs were calculated. For all analyses, statistical significance was set at P＜0.05. Statistical analyses were performed using JMP Pro, version 17 (SAS Institute, Cary, North Carolina, USA).
Table 1 presents the patients’ baseline characteristics. Higher serum IL-6 levels were significantly associated with older age, lower body mass index, chronic kidney disease, atrial fibrillation, chronic heart failure, active cancer, post-stroke pneumonia, and higher initial NIHSS scores. No significant association was found between IL-6 levels and the prevalence of intracranial or extracranial artery stenosis. Regarding stroke etiology, patients in the highest tertile group were more likely to experience a cardioembolism, whereas those in the lowest tertile group were more likely to have small vessel disease. Higher IL-6 levels were significantly associated with higher levels of creatinine, brain natriuretic peptide, and C-reactive protein, and lower estimated glomerular filtration rate, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (Table 2). Acute and preventive treatments are presented in Table 3.
| All (n = 655) | IL-6 levels | P value | |||
|---|---|---|---|---|---|
Tertile 1 (n = 216) |
Tertile 2 (n = 217) |
Tertile 3 (n = 222) |
|||
| Age, years, mean (SD) | 70.1 (13.0) | 66.2 (12.8) | 71.5 (12.9) | 72.8 (12.4) | ＜0.001 |
| Male, n (%) | 407 (62.1) | 145 (67.1) | 129 (59.4) | 133 (59.9) | 0.18 |
| BMI, kg/m2, mean (SD) | 23.7 (4.0) | 24.1 (3.5) | 23.8 (4.0) | 23.1 (4.5) | 0.046 |
| Medical history, n (%) | |||||
| Hypertension | 470 (71.8) | 150 (69.4) | 165 (76.0) | 155 (69.9) | 0.23 |
| Dyslipidemia | 321 (49.0) | 114 (52.8) | 108 (49.8) | 99 (44.6) | 0.22 |
| Diabetes mellitus | 260 (39.7) | 72 (33.3) | 90 (41.4) | 98 (44.1) | 0.056 |
| Chronic kidney disease | 212 (32.4) | 37 (17.1) | 75 (34.6) | 100 (45.0) | ＜0.001 |
| Atrial fibrillation | 132 (20.2) | 20 (9.3) | 40 (18.4) | 72 (32.4) | ＜0.001 |
| Chronic heart failure | 69 (10.5) | 9 (4.1) | 26 (12.0) | 34 (15.3) | ＜0.001 |
| Stroke | 133 (20.3) | 36 (16.7) | 46 (21.1) | 51 (23.0) | 0.24 |
| Current smoking | 121 (18.5) | 48 (22.2) | 33 (15.2) | 40 (18.0) | 0.17 |
| Excessive alcohol | 34 (5.2) | 16 (7.4) | 11 (5.1) | 7 (3.2) | 0.13 |
| Vessel imaging, n (%) | |||||
| ICAS of ＞50% or occlusion | 170 (26.0) | 59 (27.3) | 50 (23.0) | 61 (27.5) | 0.49 |
| ECAS of ＞50% or occlusion | 94 (14.4) | 29 (13.4) | 26 (12.0) | 39 (17.6) | 0.22 |
| Complication, n (%) | |||||
| Pneumonia | 31 (4.7) | 2 (0.93) | 10 (4.6) | 19 (8.6) | ＜0.001 |
| Bone fracture | 7 (1.1) | 1 (0.46) | 3 (1.4) | 3 (1.4) | 0.57 |
| Active cancer | 22 (3.4) | 2 (0.93) | 2 (0.92) | 18 (8.1) | ＜0.001 |
| Initial NIHSS, median (IQR) | 2 (1-5) | 2 (1-3) | 2 (1-4) | 4 (1-8) | ＜0.001 |
| TOAST classification, n (%) | |||||
| Atherothrombosis | 138 (21.1) | 47 (21.8) | 44 (20.1) | 47 (21.2) | ＜0.001 |
| Small vessel disease | 161 (24.6) | 68 (31.5) | 66 (30.4) | 27 (12.2) | |
| Cardioembolism | 149 (22.8) | 20 (9.3) | 49 (22.6) | 80 (36.0) | |
| Undetermined | 163 (24.9) | 70 (32.4) | 52 (24.0) | 41 (18.5) | |
| Others | 44 (6.7) | 11 (5.1) | 6 (2.8) | 27 (12.2) | |
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL; tertile 2, 2.6-6.1 pg/mL; and tertile 3, ≥ 6.2 pg/mL. Abbreviations: BMI = body mass index; ECAS = extracranial artery stenosis; ICAS = intracranial atherosclerotic stenosis; IL-6 = interleukin-6; IQR = interquartile range; NIHSS = National Institutes of Health Stroke Scale; SD = standard deviation; TOAST = Trial of Org 10172 in Acute Stroke Treatment.
| All (n = 655) | IL-6 levels | P value | |||
|---|---|---|---|---|---|
Tertile 1 (n = 216) |
Tertile 2 (n = 217) |
Tertile 3 (n = 222) |
|||
| Blood pressure, mean (SD) | |||||
| Systolic, mm Hg | 154 (27) | 154 (26) | 156 (26) | 151 (31) | 0.25 |
| Diastolic, mm Hg | 86 (17) | 88 (16) | 86 (16) | 84 (18) | 0.10 |
| Laboratory data, mean (SD) | |||||
| Creatinine, mg/dL | 0.87 (0.48) | 0.82 (0.30) | 0.85 (0.51) | 0.99 (0.75) | ＜0.001 |
| eGFR, mL/min/1.73m2 | 58.3 (25.2) | 67.1 (19.1) | 57.7 (25.4) | 50.3 (27.4) | ＜0.001 |
| HDL-C, mg/dL | 56 (18) | 59 (18) | 56 (16) | 52 (18) | ＜0.001 |
| LDL-C, mg/dL | 115 (37) | 121 (35) | 117 (35) | 107 (39) | ＜0.001 |
| TG, mg/dL | 109 (76) | 111 (76.3) | 109 (79) | 108 (77) | 0.22 |
| HbA1c, % | 6.1 (1.3) | 6 (1.2) | 6.1 (1.5) | 6.2 (1.3) | 0.29 |
| BNP, pg/mL | 63 (148) | 34 (50) | 66 (128) | 155 (403) | ＜0.001 |
| CRP, mg/dL | 0.21 (0.54) | 0.08 (0.13) | 0.21 (0.34) | 0.84 (2.90) | ＜0.001 |
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL; tertile 2, 2.6-6.1 pg/mL; and tertile 3, ≥ 6.2 pg/mL. Abbreviations: BNP = brain natriuretic peptide; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate; HDL-C = high-density lipoprotein cholesterol; IL-6 = interleukin-6; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation; TG = triglycerides.
| All (n = 655) | IL-6 levels | P value | |||
|---|---|---|---|---|---|
Tertile 1 (n = 216) |
Tertile 2 (n = 217) |
Tertile 3 (n = 222) |
|||
| Tissue plasminogen activator | 40 (6.1) | 5 (2.3) | 9 (4.1) | 26 (11.7) | ＜0.001 |
| Mechanical thrombectomy | 19 (2.9) | 3 (1.4) | 3 (1.4) | 13 (5.9) | 0.006 |
| Antiplatelet agent | 466 (71.2) | 184 (85.2) | 167 (77.0) | 115 (51.8) | ＜0.001 |
| Anticoagulant agent | 215 (32.8) | 41 (19.0) | 62 (28.6) | 112 (50.5) | ＜0.001 |
| Antihypertensive agent | 367 (56.0) | 105 (48.6) | 129 (59.5) | 133 (60.0) | 0.027 |
| Lipid lowering agent | 426 (65.0) | 153 (70.8) | 147 (67.7) | 126 (56.8) | 0.005 |
| Glucose lowering agent or insulin | 192 (29.3) | 59 (27.3) | 67 (30.9) | 66 (29.7) | 0.71 |
| Carotid endarterectomy | 6 (0.9) | 2 (0.9) | 2 (0.9) | 2 (0.9) | 1.00 |
| Carotid artery stent | 14 (2.1) | 4 (1.9) | 4 (1.8) | 6 (2.7) | 0.77 |
| Extracranial-intracranial bypass | 2 (0.3) | 2 (0.9) | 0 (0) | 0 (0) | 0.13 |
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL; tertile 2, 2.6-6.1 pg/mL; and tertile 3, ≥ 6.2 pg/mL.
Figures are expressed as n (%). Abbreviations: IL-6 = interleukin 6.
As shown in Fig.2, patients in the highest tertile group had higher rates of MACE (annual rate: 11.2 %, 10.8%, and 19.1% in the tertiles 1, tertile 2, and tertile 3 groups, respectively; log-rank P = 0.019) and all-cause deaths (annual rate: 10.7%, 9.2%, and 15.8% in the tertiles 1, tertile 2, and tertile 3 groups, respectively; log-rank P＜0.001). Regarding the incidence of stroke, there was a trend towards more in tertile 3 compared to tertile 1. After adjustments for possible confounders, the higher IL-6 levels were significantly associated with a higher risk of all-cause death (adjusted HR for tertile 3 versus tertile 1 groups, 4.01; 95% CI, 1.31-12.29) (Table 4).
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL (n = 216); tertile 2, 2.6-6.1 pg/mL (n = 217); and tertile 3, ≥ 6.2 pg/mL (n = 222).
| Major adverse cardiovascular events | |||||
| IL-6 levels | Event, n (%) |
Crude HR (95% CI) |
P value | Adjusted HR (95% CI)＊ |
P value＊ |
| Tertile 1 | 24 (11.2) | Ref. | - | Ref. | - |
| Tertile 2 | 23 (10.8) | 0.95 (0.54-1.69) | 0.87 | 0.86 (0.48-1.55) | 0.62 |
| Tertile 3 | 40 (19.1) | 1.77 (1.07-2.94) | 0.027 | 1.56 (0.87-2.77) | 0.13 |
| Stroke | |||||
| IL-6 levels | Event, n (%) | Crude HR (95% CI) |
P value | Adjusted HR (95% CI)＊ |
P value＊ |
| Tertile 1 | 23 (10.7) | Ref. | - | Ref. | - |
| Tertile 2 | 20 (9.2) | 0.86 (0.47-1.57) | 0.63 | 0.83 (0.45-1.54) | 0.56 |
| Tertile 3 | 35 (15.8) | 1.53 (0.90-2.58) | 0.12 | 1.60 (0.87-2.92) | 0.13 |
| All-cause death | |||||
| IL-6 levels | Event, n (%) | Crude HR (95% CI) |
P value | Adjusted HR (95% CI)＊ |
P value＊ |
| Tertile 1 | 4 (1.9) | Ref. | - | Ref. | - |
| Tertile 2 | 2 (0.92) | 0.50 (0.09-2.71) | 0.42 | 0.36 (0.06-2.02) | 0.24 |
| Tertile 3 | 36 (16.2) | 9.48 (3.38-26.6) | ＜0.001 | 4.01 (1.31-12.29) | 0.015 |
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL; tertile 2, 2.6-6.1 pg/mL; and tertile 3, ≥ 6.2 pg/mL.
＊Adjusted for age, sex, body mass index, diabetes mellitus, chronic kidney disease, atrial fibrillation, chronic heart failure, pneumonia, active cancer, initial National Institutes of Health Stroke Scale, Trial of Org 10172 in Acute Stroke Treatment classification, tissue plasminogen activator, and mechanical thrombectomy.
Abbreviations: CI = confidence interval; IL-6 = interleukin-6; HR = hazard ratio.
The distribution of mRS scores at one year is shown in Fig.3. Patients with higher levels of IL-6 were more likely to have a poor functional prognosis (percentages of patients with mRS score ≥ 3, 14.4%, 29.5%, and 56.8% in the tertile 1, tertile 2, and tertile 3 groups, respectively; P＜0.001). Multivariable analysis revealed that higher IL-6 levels were independently associated with a poor functional prognosis (adjusted OR for tertile 2 versus tertile 1 groups, 1.90; 95% CI, 1.10-3.30; adjusted OR for tertile 3 versus tertile 1 groups, 3.63; 95% CI, 2.06-6.41) and all-cause death (adjusted OR for tertile 3 versus tertile 1 groups, 10.59; 95% CI, 2.24-50.1) at one year (Table 5).
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL (n = 216); tertile 2, 2.6-6.1 pg/mL (n = 217); and tertile 3, ≥ 6.2 pg/mL (n = 222).
Abbreviations: IL-6 = interleukin-6; mRS = modified Rankin Scale.
| mRS ≥ 3 | ||||
| IL-6 levels | Crude OR (95% CI) | P value | Adjusted OR (95% CI)＊ | P value＊ |
| Tertile 1 | Ref. | - | Ref. | - |
| Tertile 2 | 2.50 (1.55-4.03) | ＜0.001 | 1.90 (1.10-3.30) | 0.022 |
| Tertile 3 | 7.83 (4.93-12.5) | ＜0.001 | 3.63 (2.06-6.41) | ＜0.001 |
| All-cause death | ||||
| IL-6 levels | Crude OR (95% CI) | P value | Adjusted OR (95% CI)＊ | P value＊ |
| Tertile 1 | Ref. | - | Ref. | - |
| Tertile 2 | 2.01 (0.36-11.1) | 0.42 | 1.52 (0.24-9.54) | 0.65 |
| Tertile 3 | 24.2 (5.78-101.6) | ＜0.001 | 10.59 (2.24-50.1) | 0.003 |
Patients were divided into three groups according to the tertile of serum levels of IL-6: tertile 1, ＜2.6 pg/mL; tertile 2, 2.6-6.1 pg/mL; and tertile 3, ≥ 6.2 pg/mL.
＊Adjusted for age, sex, body mass index, diabetes mellitus, chronic kidney disease, atrial fibrillation, chronic heart failure, pneumonia, active cancer, initial National Institutes of Health Stroke Scale, Trial of Org 10172 in Acute Stroke Treatment classification, tissue plasminogen activator, mechanical thrombectomy, and major adverse cardiovascular events.
Abbreviations: CI = confidence interval; IL-6 = interleukin-6; mRS = modified Rankin Scale; OR = odds ratio.
In this prospective observational study, higher serum IL-6 levels at admission were found to be independently associated with a poor functional prognosis (mRS score ≥ 3) and all-cause death at one year after stroke, even when adjusting for baseline covariates and MACE during follow-up.
Prior studies have supported the association between IL-6 levels and poor functional prognosis in patients with ischemic stroke6-9). Furthermore, a strong association between IL-6 levels and cardiovascular risk11), as well as post-stroke infections, such as post-stroke pneumonia, has also been reported12-14). However, these adverse events affect stroke outcomes, and it is unclear whether the association between IL-6 and long-term prognosis after stroke is independent of these adverse events. In the present study, serum IL-6 levels were associated with age, body mass index, chronic kidney disease, atrial fibrillation, chronic heart failure, active cancer, systemic inflammation, and stroke severity, and were also strongly associated with post-stroke pneumonia and recurrent vascular events during follow-up. Even after adjustment for these factors, serum IL-6 levels were independently associated with poor functional prognosis and mortality at one year after stroke. Our result suggests that serum IL-6 levels at stroke onset may be an independent predictor of long-term prognosis after stroke.
This independent association between IL-6 in acute stroke and long-term outcome is partly because IL-6 is a marker that reflects the broader pathophysiology not assessed in this study, but it is also possible that IL-6 itself determines long-term outcome. If so, lowering IL-6 may improve outcome.
Several studies have been reported on cardiovascular disease and IL-6 inhibitors. A previous study demonstrated that an anti-IL-6 receptor antibody promoted cognitive function recovery in stroke mice15). Furthermore, genetic evidence in humans has shown that IL-6 receptor signaling plays a causal role in the development of coronary heart disease16).
Prior studies have further shown that anti-interleukin-1b monoclonal antibody and IL-1 receptor antagonists reduce IL-6 levels15). The hypothesized mechanism is as follows: anti-IL-1b monoclonal antibody decreases IL-1 levels, which decreases IL-1-induced IL-6 levels. However, a recent clinical trial showed that IL-1 receptor antagonists were not associated with favorable outcomes on the mRS after ischemic stroke16). Prospects for therapeutic intervention for IL-6 are difficult to predict due to a lack of research.
LimitationsThis study had several limitations. First, because it was conducted in a single-center setting in Japan, the results may not be generalizable. The annual MACE rate of 13.3% was higher than those reported in previous clinical trials17, 18). This may be partly because the patients were enrolled consecutively, regardless of age, general condition, or comorbidities, and clinical trials typically select patients with a fair systemic condition. Second, the measurement of IL-6 levels was performed at a single point in this study. It has further been reported that serum IL-6 levels increase less than 6 h after the onset of acute stroke, reach a maximum within 24 h, reach a plateau at 3-4 days, and then begin to gradually decline, and that high serum IL-6 levels at stroke onset are associated with poor clinical outcomes19-21). Therefore, it was not possible to evaluate the changes in this study. Furthermore, as this study enrolled patients with cerebral infarction within one week of onset and measured their serum IL-6 levels at the time of admission, the potential influence of the time interval between stroke onset and IL-6 measurement was not evaluated. In patients who received acute treatments, such as tissue plasminogen activator administration or mechanical thrombectomy, IL-6 levels were assessed at admission after these interventions, suggesting that the treatments may have affected IL-6 levels. Third, the patients in this study had a relatively mild stroke; therefore, our results may not be applicable to patients with moderate or severe stroke. Fourth, since IL-6 is associated with multiple factors, it is possible that not all confounding factors were fully accounted for in the analysis. Finally, the backgrounds of patients with high IL-6 levels have not yet been thoroughly investigated. Therefore, these patients may have systemic inflammatory diseases or occult cancers that affect serum IL-6 levels.
This study identified independent associations among serum IL-6 levels, poor functional outcomes, and mortality in patients with ischemic stroke. Therefore, serum IL-6 may be useful as a long-term prognostic marker for stroke.
None.
This work was supported by JSPS KAKENHI (grant number JP20K07885 and JP24K10641).
The authors declare no conflicts of interest associated with this manuscript.
Conceptualization: SA, KK
Data curation: SA, TH, TM, KI, MH, ST, SW, ST
Formal analysis: SA, TH, TM
Supervision: KK, KT
Writing - original draft: SA, TH
Writing - review and editing: SA, TH, TM, KI, MH, ST, SW, ST, KK, KT
Data supporting the findings of this study are available from the corresponding author upon reasonable request.
