Clinical Study
Changes in serum interleukin-33 levels in patients with acute cerebral infarction

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Abstract

Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction.

Introduction

Acute cerebral infarction is a severe neurological disorder in humans. Inflammation is found to develop at a sufficiently early stage to participate in progressive ischemic brain injury [1]. Animal studies and clinical trials both support the hypothesis that inflammation is involved in ischemic brain damage. The inflammatory cytokines act as important immunotransmitters and have been recognized as critical mediators of the pathogenesis of ischemic brain injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Anti-inflammatory therapy effectively minimizes the infarction size and widens the therapeutic window against ischemic stroke [1], [2]. Thus, anti-inflammation treatments may help rehabilitation and functional recovery from ischemic brain damage.

Interleukin-33 (IL-33) is a newly identified member of the interleukin-1 superfamily and is expressed by multiple organs and many cell types following pro-inflammatory stimulation in humans and mice [3]. IL-33 binds to a heterodimeric receptor complex consisting of ST2 (also known as interleukin-1 receptor-like 1) and IL-1R accessory protein (IL-1RAP) and induces signaling through the Toll-interleukin-1 receptor domain of IL-1RAP [3], [4], [5]. IL-33 is a cytokine with dual functions, acting both as a traditional cytokine through the activation of the ST2 receptor complex and as an intracellular nuclear factor with transcriptional regulatory properties. Recently, IL-33 has been found to play important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system (CNS) inflammation [4], [5]. To our knowledge, its role in the pathology of acute cerebral infarction has not yet been reported.

The present study therefore aimed to explore the changes in serum IL-33 levels in patients with cerebral ischemia with different sizes of cerebral infarction. The results may help elucidate the potential roles of IL-33 in the inflammatory response of the injured brain as well as its clinical significance.

Section snippets

Clinical subjects

Sixty-two hospitalized patients with acute cerebral infarction (39 males, 23 females, mean aged 51.2 ± 6.8 years [standard deviation]; no significant sex/age differences between male and female patients, p > 0.05) were recruited from August to December 2011. All patients were diagnosed as having acute cerebral infarction using cranial CT scan or MRI. All were presenting with their first episode of cerebral infarction and received treatment within 48 hours after hospitalization in the Department of

Results

We found that the serum IL-33 levels in the large and medium infarct volume patient groups were significantly higher than the control group (p < 0.01). However, there was no significant difference in the serum IL-33 level between the small infarct volume group and the control group (p > 0.05) (Table 1). It was further found that the large infarct volume patient group had the highest serum IL-33 levels, which was significantly higher than the medium and small infarct volume groups (p < 0.05). In

Discussion

The present study investigated the early change of serum IL-33 levels in acute cerebral infarction patients within 48 hours after onset. The results showed that serum IL-33 levels increased significantly as the infarct volume increased. This finding suggests that the serum IL-33 level at the acute phase of cerebral infarction may be considered as a potential marker for future diagnosis and/or prognosis.

IL-33 binds to its receptor ST2 and induces a series of signaling pathways, which regulates

Conflict of interest/disclosure

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

Acknowledgement

We thank Medjaden Bioscience Limited for assisting in the preparation of this manuscript.

References (8)

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