Ischemic Stroke Is Associated With a Systemic Increase of Blood Mononuclear Cells Expressing Interleukin-8 mRNA

Abstract

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)-1␣, and MIP-1␤ 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; PϽ.0001). IL-8 levels in plasma correlated positively to IL-8 mRNA expression in examined patients (nϭ7) with ischemic stroke (rϭ.78, PϽ.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. (Stroke. 1998;29:462-466.)

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

“…47 In addition, the IL-8 chemokine has also been associated with the recruitment of inflammatory cells and is increased in stroke patients. 48,49 It has been associated with amplification of the secondary inflammatory process following stroke. 50,51 Finally, emerging data indicate that the cytokine IL-18, which seems to play a key role in neuroinflammation and neurodegeneration, is able to mediate delayed neuroinflammatory processes in experimental hypoxic-ischemic brain injury and is involved in stroke-induced neuroinflammation in humans (reviewed by Felderholf-Mueser et al 52 ).…”

Monocyte Chemoattractant Protein-1 Is Increased in the Cerebrospinal Fluid of Patients With Ischemic Stroke

“…6,9 The systemic increase of interleukin-8 mRNA expressing mononuclear cells and interleukin-8 levels in plasma from patients with ischemic stroke was found as well, suggesting involvement of interleukin-8 in recruiting blood polymorphonuclear leukocytes to the sites of cerebral ischemia. 10 Chemokines, together with adhesion molecules such as vascular cell adhesion molecule-1, which in soluble form was observed to increase in patients with acute ischemic stroke, 11 appear to be responsible for accumulation of inflammatory cells in ischemic stroke and to contribute with other factors, including several cytokines, to the pathomechanism of human stroke. …”

Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes

“…IL-8 release into the CSF after brain injury is associated with blood-brain barrier dysfunction (6) and nerve growth factor production (34). IL-8 is produced by astrocytes under acidosis (66), by blood mononuclear cells after ischemic stroke (35), and in neoplastic and infectious diseases of the human CNS (35). Also, a recent publication suggests that IL-8 contributes to shear flow-resistant adhesion of macrophages to vascular endothelial cells (20).…”