Tumour necrosis factor-alpha production in fibrosing alveolitis is macrophage subset specific.
BACKGROUND
Previous studies have revealed that tumour necrosis factor (TNF)-alpha is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-alpha 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-alpha 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-alpha 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 < 0.001). In addition, AMs from patients with FASSc secreted more TNF-alpha than those of patients with no FA (P = 0.003). In contrast, there were no significant differences in Mo TNF-alpha secretion between the groups. A positive correlation was found between total TNF-alpha level and number of neutrophils obtained by bronchoalveolar lavage from patients with FA (r = 0.49, P < 0.04). Finally, it was demonstrated that there was significant heterogeneity of TNF-alpha secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-alpha production.


CONCLUSIONS
By demonstrating the primary cell source of TNF-alpha in FASSc, more accurately targeted, possibly localized, anti-TNF strategies might be employed with success in the future.
Pantelidis
P
P
Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Royal Brompton Hospital & National Heart and Lung Institute, London, UK.
McGrath
D S
DS
Southcott
A M
AM
Black
C M
CM
du Bois
R M
RM
D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D014644:Genetic Variation; D006801:Humans; D016130:Immunophenotyping; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000473:pathology; D010586:Phagocytes / Q000378:metabolism / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D012016:Reference Values; D012595:Scleroderma, Systemic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha