Spontaneous production of proinflammatory cytokines by neutrophils in patients with Behcet's disease

• Published in: Ensho Vol. 20; no. 2; pp. 157 - 164
• Main Authors: Sakane, Tsuyoshi, Suzuki, Noboru, Takeno, Mitsuhiro, Shimoyama, Yoshihiro, Nagafuchi, Hiroko
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Society of Inflammation and Regeneration 29.03.2000
• Subjects: Behcet's disease; neutrophil; NF-κB; Th1 type cytokine
• ISSN: 0389-4290; 1884-4006
• DOI: 10.2492/jsir1981.20.157

Neutrophil hyperfunction plays a critical role in the development and exacerbations of Behçet disease (BD) . However, precise mechanisms responsible for the neutrophil hyperfunction in this disease have been obscure. We here studied cytokine production by neutrophils in patients with BD. We found that freshly isolated neutrophils spontaneously expressed mRNA of interleukin (IL) -1α and tumor necrosis factor (TNF) -α, in patients with BD, irrespective of their disease activity. Neutrophils from normal donors never expressed the mRNA spontaneously. A gel shift assay demonstrated that spontaneous expression of an inducible transcription factor, NF-κB in nuclei of freshly isolated neutrophils from BD patients, but not from normal controls. The data suggest that constitutive NF-κB expression may be responsible for the spontaneous expression of IL-1α and TNF-α mRNA by the neutrophils. Furthermore, neutrophils also spontaneously produced Thl cell develop-ment-promoting cytokines, IL-12 and IL-18 in BD patients with active diseases. The culture supernatants containing IL-12 and IL-18 indeed enhanced interferon-γ production of T lymphocytes. Neutrophil hyperactivity may thus boost the pathogenic Thl immune responses of this disease, leading to the acute exacerbation of inflammation in patients with BD. Our present study emphasizes the importance of spontaneous cytokine production by the neutrophils in patients with BD.