The Effects of Tumour Necrosis Factor α on Mediator Release from Human Lung

Abstract

Summary: Although tamour necrosis factor α (TNFα) may be involved in the pathology of asthma, little is known about its role in mediator release from inflammatory cells in human lung. We investigated whether TNFα induced histamine release from mast cells in human chopped lung tissue and whether it modulated antigen-induced release of histamine and leukotrienes C 4/D 4/E 4 from passively sensitized lung tissue. Spontaneous histamine release in the presence of 1 nM TNFα for up to 4 h at 37°C was not significantly different from spontaneous histamine release alone (6.1±1.3% and 6.1±1.5% of total tissue histamine at 4 h respectively; n=3). Lung tissue was passively sensitized to the house dust mite Dermatophagoides pteronyssinus by incubating it in serum from an atopic volunteer donor for 3 h at 37°C. Treatment of the sensitized lung tissue with 1 nM TNFα for 60 min prior to challenge with a low concentration (1.8 AU) of D. pteronyssinus caused a significant increase in the amount of histamine release induced by the antigen from 0.2±0.6% to 1.9±1.0% of total tissue histamine ( P=0.045, n=6). The release of leukotriene C 4/D 4/E 4 induced by the same concentration of antigen was not significantly changed by the TNFα treatment (39.5±9.1 and 55.6±17.7 pg/100 μl supernatant sample respectively; n=6). These results suggest that TNFα may be involved in potentiation of histamine release in allergic asthma, particularly in the presence of low antigen concentrations.