Effects of TNF-alpha, IFN-gamma and IL-beta on normal human bronchial epithelial cells

Several diseases affecting the airways such as asthma are associated with b oth epithelial damage and increased levels of pro-inflammatory cytokines. T o investigate the possible relation between cytokines and epithelial damage , the effects of tumour necrosis factor-alpha (TNF)-alpha, interferon gamma (IFN-gamma) and interleukin-1 beta (IL-1 beta) on normal human bronchial e pithelial cells in vitro were studied. The cells were exposed to these cytokines for 48 or 72 h, followed by morph ological, immunohistochemical and metabolic studies. Transmission and scanning electron microscopical analyses demonstrated dama ge to the mitochondria and an increase in cell processes induced by the cyt okines. The use of antibodies against desmosomal cytokeratin showed a decre ase in desmosome formation in IFN-gamma-exposed cells. Decreased glucose ox idation rate and increased accumulation of nitric oxide were found in cytok ine-exposed cells. N-omega-monomethyl-L-arginine (L-NMMA) reduced nitrite p roduction. X-ray microanalysis showed an increase in the intracellular sodi um/potassium ratio of the cells after exposure to cytokines, which is an in dication of cell damage. The cytokines induced both necrosis and apoptosis to varying degrees. IFN-gamma and TNF-alpha generally potentiate each other 's effects. In conclusion tumour necrosis factor-alpha and interferon gamma, and to a l esser extent interleukin-1 beta, can cause damage to epithelial cells, whic h may be a factor involved in epithelial shedding in airway diseases.