Human alveolar macrophages (AM) are susceptible to infection with respiratory syncytial virus (RSV), but the infection is abortive after the initial cycles of virus replication. We have investigated if RSV infection of AM results in the production of cytokines TNF, IL-6, and IL-8, all of which may modulate inflammatory and immune responses to the virus, as well as may directly protect respiratory epithelial cells against spread of infection. A semiquantitative PCR technique was employed to investigate the induction and expression of cytokine mRNA at various times after infection. Within 1 hour after interaction with RSV, increased mRNA levels were found for all three cytokines. Peak expression of the mRNAs occurred at 3-6 hours. The virus most effectively induced TNF expression > IL-6mRNA > IL-8 mRNA as compared to cytokine mRNA expression induced by bacterial endotoxin (1 microgram/ml). Inactive virus was almost as effective as live virus in inducing and maintaining increased IL-6 and IL-8 mRNA over 16 hours, while live RSV was necessary for TNF mRNA expression. Protein concentrations of the different cytokines in the supernatants of infected AM reflected the increased levels of mRNAs in the cells. Despite the high levels of cytokines with possible antiviral activity (TNF and IL-6) in the AM supernatants, neither supernatants nor recombinant TNF protected bronchial epithelial cells (BEAS) from infection with RSV. However, TNF,IL-1, and RSV, but not IL-6, induced IL-8 and IL-6 mRNA expression by the BEAS, suggesting that cytokines produced by RSV infected AM are more important in modulating the inflammatory response in infection than directly interfering with virus infection/replication.