Exaggerated neurogenic inflammation and substance p receptor upregulation in RSV-infected weanling rats

Respiratory syncytial virus (RSV) infection in adult rats causes exaggerate d inflammation after sensory nerve stimulation in the extrapulmonary, but n ot in the intrapulmonary airways. The goal of this study was to analyze neu rogenic inflammation in weanling F-344 rats infected with RSV 18 +/- 2 d af ter birth. Five days after RSV inoculation, the extravasation of Evens blue -labeled albumin after nerve stimulation was significantly greater in the i ntrapulmonary airways of RSV-infected weanling rats than in pathogen-free c ontrol rats. In contrast, no difference was found in the extrapulmonary air ways. The level of messenger RNA (mRNA) encoding the substance P (SP) recep tor (neurokinin 1 [NK1]) increased fourfold in RSV-infected lungs, whereas mRNA encoding the VIPR1 receptor for the antiinflammatory vasoactive intest inal peptide (VIP) increased to a much lesser degree. mRNAs encoding the ot her neurokinin (NK2) and VIP (VIPR2) receptors were not affected by the vir us. Selective inhibition of the NK1 receptor abolished neurogenic inflammat ion in RSV-infected intrapulmonary airways. Also, neurogenic inflammation a nd NK1 receptor upregulation in infected lungs were inhibited by prophylaxi s with a monoclonal antibody against RSV. These data suggest that RSV lower respiratory tract infection makes the intrapulmonary airways of young rats abnormally susceptible to the proinflammatory effects of SP by selectively upregulating the expression of NK1 receptors.