Changes in pulmonary histology and exfoliated bronchoalveolar cells induced by in vivo introduction of the tumor necrosis factor-alpha gene

An inflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been impli cated in the pathogenesis of inflammatory lung diseases such as interstitia l pneumonia (IP). To clarify the role of the inflammatory cytokine in the p athogenesis of lung inflammation, we introduced a murine TNF-alpha gene int o murine lungs by the hemagglutinating virus of Japan (HVJ)-liposome method . Seven days after the TNF-alpha gene introduction resulted in marked cellu lar infiltration of alveoli, and mild histological change was observed 28 d ays after the gene introduction. Electron microscopic analysis revealed min imal deposition of collagen fibrils. Analysis of the BAL revealed that the total cell number was markedly increased 3 and 7 days after the gene introd uction, and more than 90% of the cells were macrophages. The increase in th e cell number was returned to below the normal level 28 days after the gene introduction. During the development of IP, TNF-alpha may regulate patholo gic change of the pulmonary interstitium and alveolar cells.