| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 (<it>P</it> = 0.0002) or normal healthy controls (<it>P</it> < 0.001). In addition, AMs from patients with FASSc secreted more TNF-α than those of patients with no FA (<it>P</it> = 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 (<it>r</it> = 0.49, <it>P</it> < 0.04). Finally, it was demonstrated that there was significant heterogeneity of TNF-α secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-α production.</p> <p>Conclusion</p> <p>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.</p>
|
|---|
