Serum Interleukin‐37 Increases in Patients after Ischemic Stroke and Is Associated with Stroke Recurrence

Abstract

Background. This study seeks to assess interleukin-37 (IL-37) serum level in acute ischemic stroke and the value of predicting 3-month stroke recurrence and functional outcome in acute ischemic stroke. Methods. From January 1, 2018, to June 30, 2019, all consecutive first-ever acute ischemic stroke patients from our hospital, China, were included. Serum samples, clinical information, and stroke severity (defined by the National Institute of Health stroke scale (NIHSS) score) were collected at baseline. Serum IL-37 level was measured by the enzyme-linked immunosorbent assay (ELISA) method. Functional impairment (defined by the modified Rankin scale (mRS)) and recurrent stroke were assessed 3 months after admission. The relation of IL-37 with either clinical severity at baseline, unfavorable functional outcome, or stroke recurrence at follow-up was evaluated by logistic regression analysis, and the results were presented as odds ratios (OR) with 95% confidence intervals (CI). Results. Three hundred and ten stroke patients were included. The median IL-37 serum level in those patients was 344.1 pg/ml (interquartile range (IQR), 284.4-405.3 vs. control cases: 122.3 pg/ml (IQR, 104.4-1444.0); P < 0.001 ). At 3 months, a total of 36 (11.6%) patients had a stroke recurrence. IL-37 serum levels in those patients were higher than in those patients without stroke recurrence (417.0 pg/ml (IQR, 359.3-436.1) vs. 333.3 pg/ml (279.0-391.0)). In a logistic model adjusted for other factors, IL-37 in the highest quartile (>405.3 pg/ml) was still associated with recurrent stroke ( OR = 3.32 ; 95 % CI = 2.03 – 6.13 ; P < 0.001 ). IL-37 could promote the NIHSS score (area under the curve (AUC) of the IL-37/NIHSS, 0.75; 95% CI, 0.67–0.83; P < 0.001 ), corresponding to a difference of 0.085 (0.005). Serum IL-37 increases in patients with poor outcome, and an IL-37 in the highest quartile is related to poor outcome ( OR = 4.85 ; 95 % CI = 3.11 − 8.22 ; P < 0.001 ). Conclusion. Serum IL-37 increased in patients after ischemic stroke and was associated with stroke recurrence events and poor stroke outcomes. Large randomized controlled trials should be carried out to confirm whether IL-37 lowering treatment improves stroke prognosis.

Interleukins and Ischemic Stroke

“…Increased serum IL-34 levels may be a novel diagnostic and prognostic biomarker in patients with acute ischemic stroke ( 173 ). Increased serum IL-37 in ischemic stroke patients is correlated with stroke recurrence ( 174 ) and 3-month functional prognosis ( 175 ). However, another study has illustrated that IL-37 exert protective effects by modulating post-stroke inflammation in the brain and periphery ( 176 ).…”

A machine learning model for visualization and dynamic clinical prediction of stroke recurrence in acute ischemic stroke patients: A real-world retrospective study

“…In addition, other serum biomarkers, such as serum Copeptin levels, are associated with recurrent stroke events and are predictors of severity at admission and 1-year stroke recurrence in stroke patients ( Tang et al, 2017 ). In addition, other biomarkers such as serum fatty acid binding protein 4 (FABP4) ( Li et al, 2019 ), serum CXCL12 levels ( Gu et al, 2016 ), interleukin-37 ( Zhang et al, 2021 ), and cystatin C ( Liu et al, 2021 ) have been reported to be associated with stroke recurrence.…”

Circulating interleukin-37 declines with aging in healthy humans: relations to healthspan indicators and IL37 gene SNPs

“…Most studies of IL-37 in humans have focused on its role in inflammatory disorders, each of which is characterized by excessive immune activation, e.g., rheumatoid arthritis, systemic lupus erythematosus, and atherosclerosis. In these states, circulating IL-37 levels are elevated relative to healthy controls [ 16 , 32 , 33 , 35 , 38 , 46 , 50 , 54 , 64 , 66 , 67 , 69 , 71 ], presumably as a compensatory physiological response to mitigate the impact of increases in circulating pro-inflammatory cytokines [ 16 , 66 , 67 ]. Indeed, under such conditions, circulating IL-37 often correlates with concentrations of IL-6, TNF⍺, CRP, and/or other pro-inflammatory cytokines [ 16 , 31 , 32 , 46 , 66 , 69 ], as well as with markers of disease severity or progression [ 31 , 38 , 38 , 67 , 71 ].…”