Previous studies have shown that the epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), members of the EGF growth factor family, regulate processes involved in airway repair after injury. Our studies were conducted to determine whether EGF and TGF-alpha directly control processes involved in the pathogenesis of airway inflammation and/or modulate the inflammatory effects of TNF-alpha in the airway mucosa. We have found that these cell growth factors directly induced interleukin-8 (IL-8) production by an immortalized human bronchial epithelial cell line (BEAS-2B cells). Furthermore, EGF and TGF-alpha enhanced tumor necrosis factor-alpha (TNF-alpha) induced IL-8 production by BEAS-2B cells. On the other hand, EGF but not TGF-alpha increased viral replication by BEAS-2B cells exposed to HRV-14. Moreover, TNF-alpha increased viral replication in the presence of EGF but not TGF-alpha. In conclusion, this study demonstrates that both EGF and TGF-alpha play an active role in the pathogenesis of airway inflammation.