ISCHEMIC STROKE IS ASSOCIATED WITH A SYSTEMIC INCREASE OF BLOOD MONONUCLEAR-CELLS EXPRESSING INTERLEUKIN-8 MESSENGER-RNA

Background and Purpose-Ischemic brain injury secondary to an arterial occlusion is characterized by acute local inflammation. Blood polymorp honuclear leukocytes (PMNL), primarily neutrophils, adhere to endothel ial cells and rapidly invade the injured brain after the arterial occl usion. This neutrophilic invasion might correlate with the production of certain chemoattractants by blood mononuclear cells (MNC). We evalu ated mRNA expression of the CXC chemokine interleukin (IL)-8, and the CC chemokines monocyte chemoattractant protein-1, macrophage inflammat ory protein (MIP)-1 alpha, and MIP-1 beta in blood MNC from patients w ith ischemic stroke. Methods-Peripheral blood was obtained at 8 AM on days 1 to 7 (mean, day 3) after onset of symptoms. In situ hybridizati on with radiolabeled synthetic oligonucleotide probes for the chemokin es 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 o f IL-8 mRNA expressing blood MNC, regardless of the time interval betw een onset of clinical symptoms and examination. There was a marked dif ference between patients with ischemic stroke and healthy subjects (me dian, 6228 versus 885 positive cells per 10(5) MNC; P<.0001). IL-8 lev els in plasma correlated positively to IL-8 mRNA expression in examine d patients (n=7) with ischemic stroke (r=.78, P<.05). In contrast, mRN A expression for the CC chemokines showed no significant difference be tween patients with ischemic stroke and healthy control subjects. Conc lusions-This study demonstrated a systemic increase of IL-8 mRNA expre ssing MNC and IL-8 levels in plasma from patients with ischemic stroke , suggesting that IL-8 could be involved in recruiting blood PMNL to t he sites of cerebral ischemia.