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Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic
N Kostulas1, S H Pelidou, P Kivisäkk
1Neuro-Angiological Research Center, Division of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. Nikolakis@hotmail.com
Background And Purpose:
Ischemic brain injury secondary to arterial occlusion is characterized by acute local inflammation, which involves accumulation of polymorphonuclear neutrophils (PMN). Factors that influence the recruitment of PMN could represent new therapeutic targets in acute stroke. In this prospective study we evaluated numbers of peripheral blood mononuclear cells (PBMC) expressing mRNA for interleukin (IL)-1beta, IL-8, and IL-17 and macrophage inflammatory protein-1alpha (MIP-1alpha) after ischemic stroke.
Methods:
Peripheral blood was obtained on days 1 to 3, 4 to 10, and 20 to 31 after onset of symptoms. In situ hybridization with radiolabeled synthetic oligonucleotide probes was adopted to measure cytokine mRNA expression in PBMC. Plasma and cerebrospinal fluid levels of IL-8 were measured by an enzyme-linked immunosorbent assay.
Results:
Most patients with ischemic stroke had clearly elevated numbers of IL-1beta, IL-8, and IL-17 mRNA expressing PBMC 1 to 3 days after onset of symptoms compared with healthy individuals (P<0. 0001 for all comparisons). At follow-up after 20 to 31 days, numbers of IL-8 mRNA expressing PBMC were lower than during the acute stage (P<0.001), but only IL-1beta and IL-17 mRNA expression had returned to the level of the healthy individuals. Numbers of MIP-1alpha mRNA expressing PBMC did not differ between patients with ischemic stroke and healthy individuals at any time point. A correlation was observed between numbers of IL-1beta, IL-8, and IL-17 mRNA expressing PBMC and the degree of neurological impairment as measured by the Scandinavian Stroke Scale 1 to 3 days after onset of symptoms (r=0.5; P<0.01 for all correlations).
Conclusions:
A longitudinal study of patients with ischemic stroke revealed systemic increases of levels of IL-1beta, IL-8, and IL-17 that correlated with Scandinavian Stroke Scale scores. IL-8 levels were further increased in cerebrospinal fluid.
Insights
Ischemic stroke elevates specific inflammatory markers like IL-1beta, IL-8, and IL-17 in peripheral blood mononuclear cells (PBMC). These elevated cytokine levels correlate with stroke severity, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Inflammation Research
Background:
- Ischemic stroke involves acute inflammation with polymorphonuclear neutrophil (PMN) accumulation.
- Understanding PMN recruitment factors may reveal novel therapeutic targets for acute stroke.
Purpose of the Study:
- To evaluate peripheral blood mononuclear cells (PBMC) expressing mRNA for interleukin (IL)-1beta, IL-8, IL-17, and macrophage inflammatory protein-1alpha (MIP-1alpha) in ischemic stroke patients.
Main Methods:
- Prospective study analyzing PBMC mRNA expression via in situ hybridization.
- Blood samples collected at 1-3, 4-10, and 20-31 days post-stroke.
- Enzyme-linked immunosorbent assay used for plasma and cerebrospinal fluid IL-8 levels.
Main Results:
- Elevated IL-1beta, IL-8, and IL-17 mRNA in PBMC observed 1-3 days after stroke onset (P<0.0001).
- MIP-1alpha mRNA levels did not differ between patients and controls.
- Cytokine mRNA levels correlated with neurological impairment (Scandinavian Stroke Scale scores).
Conclusions:
- Ischemic stroke leads to systemic increases in IL-1beta, IL-8, and IL-17.
- Elevated cytokine levels correlate with stroke severity.
- Increased IL-8 levels were also found in cerebrospinal fluid.