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Ischemic stroke is associated with a systemic increase of blood mononuclear cells expressing interleukin-8 mRNA
N Kostulas1, P Kivisäkk, Y Huang
1Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Nikolakis@hotmail.com
Background And Purpose:
Ischemic brain injury secondary to an arterial occlusion is characterized by acute local inflammation. Blood polymorphonuclear leukocytes (PMNL), primarily neutrophils, adhere to endothelial cells and rapidly invade the injured brain after the arterial occlusion. This neutrophilic invasion might correlate with the production of certain chemoattractants by blood mononuclear cells (MNC). We evaluated mRNA expression of the CXC chemokine interleukin (IL)-8, and the CC chemokines monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta in blood MNC from patients with ischemic stroke.
Methods:
Peripheral blood was obtained at 8 AM on days 1 to 7 (mean, day 3) after onset of symptoms. In situ hybridization with radiolabeled synthetic oligonucleotide probes for the chemokines was adopted to measure chemokine mRNA expression in MNC. An enzyme-linked immunosorbent assay for IL-8 was used to measure IL-8 levels in plasma.
Results:
Most patients with ischemic stroke had high numbers of IL-8 mRNA expressing blood MNC, regardless of the time interval between onset of clinical symptoms and examination. There was a marked difference between patients with ischemic stroke and healthy subjects (median, 6228 versus 885 positive cells per 10(5) MNC; P<.0001). IL-8 levels in plasma correlated positively to IL-8 mRNA expression in examined patients (n=7) with ischemic stroke (r=.78, P<.05). In contrast, mRNA expression for the CC chemokines showed no significant difference between patients with ischemic stroke and healthy control subjects.
Conclusions:
This study demonstrated a systemic increase of IL-8 mRNA expressing MNC and IL-8 levels in plasma from patients with ischemic stroke, suggesting that IL-8 could be involved in recruiting blood PMNL to the sites of cerebral ischemia.
Insights
Patients with ischemic stroke show increased interleukin-8 (IL-8) mRNA in blood cells and plasma. This suggests IL-8 may recruit neutrophils to the brain during ischemic injury.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Ischemic stroke causes brain injury and inflammation.
- Neutrophils infiltrate the brain after arterial occlusion.
- Mononuclear cells may produce chemoattractants that recruit neutrophils.
Purpose of the Study:
- To evaluate mRNA expression of CXC chemokine interleukin-8 (IL-8) and CC chemokines in blood mononuclear cells (MNC) from ischemic stroke patients.
- To determine if IL-8 plasma levels correlate with its mRNA expression in MNC.
Main Methods:
- Blood samples collected from ischemic stroke patients (days 1-7 post-symptom onset).
- In situ hybridization used to measure chemokine mRNA expression in MNC.
- Enzyme-linked immunosorbent assay (ELISA) measured plasma IL-8 levels.
Main Results:
- Significantly higher IL-8 mRNA-expressing MNC found in ischemic stroke patients compared to healthy subjects.
- Plasma IL-8 levels positively correlated with IL-8 mRNA expression in patients.
- No significant difference in CC chemokine mRNA expression between patients and controls.
Conclusions:
- Ischemic stroke is associated with a systemic increase in IL-8 mRNA-expressing MNC and plasma IL-8.
- IL-8 may play a role in recruiting blood neutrophils to cerebral ischemia sites.