Respiratory syncytial virus upregulates expression of the substance P receptor in rat lungs

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infant s. The first goal of this study was to determine whether the infection foll owing endotracheal inoculation of RSV in Fischer 344 rats results in increa sed inflammatory responses to substance P (SP) either released by capsaicin from sensory nerves or injected into the circulation. Five days after inoc ulation, the extravasation of Evans blue-labeled albumin after capsaicin or SP was significantly greater in RSV-infected airways than in pathogen-free controls. The peptide-degrading activity of the regulatory enzyme neutral endopeptidase was unaffected by RSV. However, SP(NK1) receptor mRNA levels increased fivefold in RSV-infected lungs, and the density of SP binding sit es in the bronchial mucosa increased threefold. These data suggest that RSV makes the airways abnormally susceptible to the proinflammatory effects of SP by upregulating SP(NK1) receptor gene expression, thereby increasing th e density of these receptors on target cells. This effect may contribute to the inflammatory reaction to the virus and could be a target for the thera py of RSV disease and its sequelae.