Tumour necrosis factor-α production in fibrosing alveolitis is macrophage subset specific

Abstract

Abstract Background Previous studies have revealed that tumour necrosis factor (TNF)-α is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-α secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. In particular, we wished to assess whether TNF-α levels differ between SSc patients with FA (FASSc) and a nonfibrotic group. Methods The reverse haemolytic plaque assay was used to evaluate the secretion of cytokine at a single cell level while immunostaining allowed subtyping of AMs and Mos. Results This study demonstrated a difference in total TNF-α levels produced by AMs when the levels in subjects with FA (cryptogenic FA and FASSc) were compared to levels in either SSc patients without FA (P = 0.0002) or normal healthy controls (P P = 0.003). In contrast, there were no significant differences in Mo TNF-α secretion between the groups. A positive correlation was found between total TNF-α level and number of neutrophils obtained by bronchoalveolar lavage from patients with FA (r = 0.49, P Conclusion By demonstrating the primary cell source of TNF-α in FASSc, more accurately targeted, possibly localized, anti-TNF strategies might be employed with success in the future.

Keywords

• fibrosing alveolitis
• haemolytic plaque
• macrophages
• monocytes
• systemic sclerosis
• tumour necrosis factor (TNF)-α