Leukocyte Activation Detected by Increased Plasma Levels of Inflammatory Mediators in Patients With Ischemic Cerebrovascular Diseases

Abstract

Leukocytes have been implicated in the development of ischemic atherosclerotic vascular diseases. In a prospective study we investigated whether the plasma concentrations of inflammatory mediators, ie, proteases and cytokines, as markers for systemic leukocyte activation, are increased in patients with acute ischemic cerebrovascular diseases. Using enzyme-linked immunosorbent assays, we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil proteinase 4 (NP4), tumor necrosis factor-alpha (TNF), and soluble TNF receptor protein-1 p55 (sTNFR-1) in 120 patients with acute ischemic cerebrovascular insult (72 with stroke and 48 with transient ischemic attack [TIA]) and in 35 age- and sex-matched healthy subjects. Compared with the control group, plasma NGAL levels were higher in the stroke group (P < .0001) and the TIA group (P < .01); plasma NP4 levels were higher in the stroke group (P < .0001) and the TIA group (P < .01); and plasma sTNFR-1 levels were higher in the stroke group (P < .04). There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 (r = .32; P = .005) and NGAL (r = .40; P = .0001) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 (r = .35; P = .001) and NGAL (r = .34; P = .002). Our study demonstrated that markers for systemic leukocyte activation, ie, plasma levels of cytokines and proteases, were higher in patients with acute ischemic cerebrovascular disease than in healthy control subjects. Activated leukocytes and leukocytic mediators may have an important role in acute cerebrovascular ischemia and its consequences.