Viral respiratory infections rapidly increase vascular permeability, which leads to the transudation of serum proteins into airway secretions and tissues. To determine whether this process activates airway epithelial cells, bronchial epithelial cells were incubated with serum, and interleukin (IL)-8 secretion and gene expression were examined. As little as 0.1% serum significantly enhanced IL-8 secretion, and maximal secretion (65 +/- 4 ng/ml, 48 h) was observed with 10% serum. Low-density lipoprotein, but not albumin or immunoglobulin G, augmented bronchial epithelial IL-8 secretion, which was partially blocked by a monoclonal antibody specific for the low-density lipoprotein receptor. The IL-8-inducing activity of plasma was also augmented by clotting and platelet activation. Mechanistically, serum activated nuclear factor-kappaB and increased the stability and steady state levels of IL-8 mRNA. In summary, specific components of serum are potent activators of IL-8 mRNA and secretion, and the increased IL-8 production is likely to be a result of both increased transcription and mRNA stability. This effect may represent an innate mechanism for the recruitment of neutrophils to the airway in response to noxious stimuli, such as viral infections, that increase vascular permeability.