Submitted to: Interscience Conference on Antimicrobial Agents & Chemotherapy Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 7/28/2007
Publication Date: 9/30/2006
Citation: Meyerholz, D.K., Gallup, J.M., Lazic, T., Macedo, M.M., Lehmkuhl, H.D., Ackermann, M.R. 2006. Pretreatment with recombinant human vascular endothelial growth factor reduces virus replication and inflammation in a peri-natal lamb model of RSV infection [abstract]. Interscience Conference on Antimicrobial Agents & Chemotherapy Proceedings. September 30, 2006, San Francisco, California. p. 461.
Technical Abstract: Vascular endothelial growth factor (VEGF) is increasingly recognized as a perinatal regulator of lung maturation and surfactant protein expression. Innate immune components including surfactant proteins A and D, and beta defensins have putative antimicrobial activity against pulmonary pathogens including respiratory syncytial virus (RSV). Preterm and young infants are at increased risk for pulmonary immaturity characterized by insufficient surfactant production as well as increased risk for severe manifestations of RSV infection. Our hypothesis is that VEGF pretreatment therapy would increase innate immune gene expression and decrease RSV disease in the perinatal lamb RSV model. Newborn lambs were pretreated with VEGF, betamethasone or saline, and then inoculated with RSV or sterile media. Tissues were collected at five days post inoculation corresponding to the initiation of severe lesions and peak viral replication. In control lambs, pretreatment with VEGF caused an increase in sheep beta defensin 1 (SBD1) mRNA expression, but no alteration in surfactant proteins A and D were detected. In RSV-infected lambs, VEGF therapy increased the mean daily body temperature, decreased airway neutrophil exudate and reduced RSV replication compared to betamethasone or saline pretreatment. Furthermore, VEGF therapy significantly mitigated RSV-induced increase in SP-A mRNA expression and decrease in SP-D mRNA expression. This novel study demonstrates VEGF pretreatment mitigates RSV disease and in addition VEGF regulation of innate immune genes is dependent on RSV infection status.