The effects of tumour necrosis factor alpha on mediator release from human lung

Although tumour necrosis factor alpha (TNF alpha) 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 TNF alpha induced histamine release from mast cells in human chopped lung tissue and whether it modulated antigen-induced release of histamine and leukotrienes C4/D4/E4 from passively sensitized lung tissue. Spontaneous histamine release in the presence of 1 nM TNF alpha for up to 4 h at 37 degrees C was not significantly different from spontaneous histamine release alone (6.1 +/- 1.3% and 6.1 +/- 1.5% of total tissue histamine at 4h 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 degrees C. Treatment of the sensitized lung tissue with 1 nM TNF alpha 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 C4/D4/E4 induced by the same concentration of antigen was not significantly changed by the TNF alpha treatment (39.5 +/- 9.1 and 55.6 +/- 17.7 pg/100 microliters supernatant sample respectively; n = 6). These results suggest that TNF alpha may be involved in potentiation of histamine release in allergic asthma, particularly in the presence of low antigen concentrations.