Neutrophil chemotaxis in Wegeners granulomatosis and idiopathic pulmonary fibrosis

نویسندگان

  • Alex G Richter
  • Gavin D Perkins
  • Amit Chavda
  • E Sapey
  • Lorraine Harper
  • David R. Thickett
چکیده

Background: The presence of anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener’s granulomatosis (WG), implicate the neutrophil as a key effector cell. Previous studies have reported elevated neutrophil counts in the lung although the determinants of neutrophil chemotaxis in the WG lung are unknown. Methods: BALF cell counts, myeloperoxidase (MPO) and chemokines were measured in 27 patients with WG, 20 disease controls with idiopathic pulmonary fibrosis (IPF) and 6 healthy controls. CXCL-8, IL-1β, ENA-78, G-CSF and GM-CSF were measured by ELISA. The neutrophil chemotactic potential of BALF was investigated using the under agarose method and specific antibodies examined the role of CXCL-8 and IL-1β. Results: WG BALF had an increased neutrophil percentage and elevated MPO, CXCL-8 and G-CSF concentrations compared with healthy controls. Chemotaxis of control neutrophils towards BALF from patients with active (p=0.006) and remission WG (p=0.077) and IPF patients (p=0.001) was increased compared with normal controls. BALF induced chemotaxis correlated with BALF IL-1ß (r=0.761,p=0.001) and CXCL-8 (r=0.640,p=0.012) in WG and was inhibited by anti-CXCL-8 (85%, p<0.001) and antiIL-1β (69%, p<0.001). Conclusions: Our study confirms a neutrophilia and pro-inflammatory alveolar milieu that persists in clinical remission. CXCL-8 and IL-1β appear to play important roles in the neutrophil chemotactic response to BALF.

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تاریخ انتشار 2011