Interleukin-8 (IL-8) is a chemokine that has been shown to be a potent chemoattractant for polymorphonuclear neutrophils from the vascular compartment into the pleural space during infectious pleural effusions. Mesothelial cells express the viral receptors Toll-like receptor 3 (TLR3), RIG-I, and MDA5. Activation of these receptors by viral RNA exemplified by poly (I:C) RNA leads to a time- and dose-dependent increase of mesothelial IL-8 synthesis. To show the specific effect of viral receptors, knockdown experiments with short interfering RNA specific for TLR3, RIG-I and MDA5 were performed. This novel finding of functional expression of these viral sensors on human mesothelial cells may indicate a novel link between viral infections and mesothelial inflammation and indicates a pathophysiologic role of viral receptors in these processes.