Plasma levels and skin-eosinophil-expression of vascular endothelial growth factor in patients with chronic urticaria

BACKGROUND: Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine-releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU. METHODS: Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F(1+2) were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP). RESULTS: Plasma VEGF concentrations were higher in CU patients (8.00 +/- 0.90 pmol/l) than in controls (0.54 +/- 0.08 pmol/l) (P = 0.0001) and tended to parallel both the severity of CU and to correlate with F(1+2) levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST-positive than in APST-negative patients (P = 0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF (P = 0.002) that colocalized with ECP, a classic eosinophil marker. CONCLUSIONS: VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin.