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 both epithelial damage and increased levels of pro-inflammatory cytokines. To 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-1beta) on normal human bronchial epithelial cells in vitro were studied. The cells were exposed to these cytokines for 48 or 72 h, followed by morphological, immunohistochemical and metabolic studies. Transmission and scanning electron microscopical analyses demonstrated damage to the mitochondria and an increase in cell processes induced by the cytokines. The use of antibodies against desmosomal cytokeratin showed a decrease in desmosome formation in IFN-gamma-exposed cells. Decreased glucose oxidation rate and increased accumulation of nitric oxide were found in cytokine-exposed cells. Nomega-monomethyl-L-arginine (L-NMMA) reduced nitrite production. X-ray microanalysis showed an increase in the intracellular sodium/potassium ratio of the cells after exposure to cytokines, which is an indication 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 lesser extent interleukin-1beta, can cause damage to epithelial cells, which may be a factor involved in epithelial shedding in airway diseases.

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