Interleukin-8 Production of Neutrophils and Inhibitory Effects of FK506 in Behcet's Disease

Abstract

While the etiology of Behcet's disease is still unknown, it is believed that functional abnormalities of neutrophils, such as increases in the migration and production of active oxygen, are intimately involved in the pathogenesis of the disease. This study was undertaken to examine the interleukin-8 (IL-8) production of peripheral neutrophils, focusing on the fact that the IL-8 activates neutrophil migration and enhances their function, and to examine the inhibitory effects of FK506 (an immunosuppressive agent) on neutrophil production of IL-8. Peripheral neutrophil specimens were collected from patients with Behcet's disease and healthy persons, and divided into a group stimulated by lipopolysaccharide (LPS) (LPS-stimulated group) and a group not stimulated by it (non-stimulated group). IL-8 secretion was measured in the both groups to assess the expression of IL-8 mRNA. In addition, FK506 was added to the LPS-stimulated culture to measure IL-8 secretion by neutrophils. The results showed increased neutrophil production of IL-8 in the Behcet's disease group and expression of IL-8 mRNA even in the non-stimulated group. The IL-8 production was shown to be inhibited by FK506. These findings suggest that Behcet's disease is associated with in vivo priming of peripheral neutrophils, implying that IL-8 produced by neutrophils plays a role in the pathogenesis of Behcet's disease. In addition, FK506 may have an inhibitory effection neutrophil IL-8 production as a mechanism in Behcet's disease