Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke

Abstract

During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0−2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3−6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.

Keywords: National Institutes of Health Stroke Scale; interleukin-6; ischemic stroke; modified Rankin Scale; tumor necrosis factor.

Scheme 1

The general study design.

Figure 1

Correlations between biomarkers. Statistically, significant links are marked in colour (correlation values are entered in tiles).

Figure 2

ROC curves showing sensitivity and specificity of IL-6 measurements for good functional outcome: (a) IL-6 < 4.5 h; on dismission (cut-off point ≤ 7.11 pg/mL, sensitivity 88.6%, specificity 83.3%), (b) IL-6 < 4.5 h; after three months (cut-off point ≤ 6.54 pg/mL, sensitivity 77.3%, specificity 93.3%), (c) IL-6 < 4.5 h; after a year (cut-off point ≤ 8.55 pg/mL, sensitivity 95.3%, specificity 100%), (d) IL-6 within 24 h on dismission (cut-off point ≤ 8.220 pg/mL, sensitivity 85.7%, specificity 100%), (e) IL-6 within 24 h; after three months (cut-off point ≤ 8.94 pg/mL, sensitivity 78.1%, specificity 75.0%), (f) IL-6 within 24 h; after a year (cut-off point ≤ 8.94 pg/mL, sensitivity 78.2%, specificity 75.0%).

Figure 3

ROC curves showing sensitivity and specificity of TNF-α measurements for good functional outcome: (a) TNF-α < 4.5 h; after three months (cut-off point ≤ 39.94 pg/mL, sensitivity 62.8%, specificity 100%), (b) TNF-α < 4.5 h; after a year (cut-off point ≤ 42.54 pg/mL, sensitivity 62.8%, specificity 100%), (c) TNF-α within 24 h; after three months (cut-off point ≤ 60.14 pg/mL, sensitivity 96.7%, specificity 50.0%), (d) TNF-α within 24 h; after a year (cut-off point ≤ 60.14 pg/mL, sensitivity 60.1%, specificity 100%).

Figure 4

Inflammatory biomarkers by subtypes of stroke. Abbreviations: IL-6 (0)—interleukin 6 within 4.5 h; TNF-α (0)—tumour necrosis factor within 4.5 h; TNF-α (1)—tumour necrosis factor within 24 h; LACI—lacunar cerebral infarct; PACI—partial anterior circulation infarct; POCI—posterior circulation infarction.

Figure 5

The percentage of deaths among patients after stroke with an increase in the biomarker value. Abbreviations: IL-6 (0)—interleukin 6 within 4.5 h; IL-6 (1)—interleukin 6 within 24 h; IL-6 (2)—interleukin 6 within 7 days; TNF-α (0)—tumour necrosis factor within 4.5 h; TNF-α (1)—tumour necrosis factor within 24 h; TNF-α (2)—tumour necrosis factor within 7 days.

Scheme 2

The summary of the study.