Novel pathways in the pathogenesis of respiratory syncytial virus disease.
Respiratory syncytial virus (RSV) is a leading cause of severe respiratory infections in infants and children. Extensive research in past decades has expanded our knowledge regarding the specific mechanisms involved in the pathogenesis of RSV bronchiolitis and subsequent chronic obstructive airway disease. Studies of RSV infection are performed in humans, cell culture models, and animal models, each with their own specific limitations. A recently developed murine model in which pulmonary dysfunction can be monitored and quantified appears to add a powerful tool for the study of specific pathogenic mechanisms of experimental RSV infections. Both immunologic and nonimmunologic factors have been implicated in the pathogenesis of RSV-induced diseases. Recently, a hypothesis that RSV bronchiolitis may be the result of production of Th2-type cytokines has become popular. There are, however, studies in human infants with RSV as well as in RSV-infected mice that suggest this theory is incorrect, or at least an oversimplification. There is compelling evidence that cells producing interferon gamma may contribute to RSV-induced wheezing, possibly through induction of leukotriene release. Among the nonimmunologic factors, pulmonary surfactant has recently attracted attention, especially because of the therapeutic implications for infants with severe bronchiolitis. A better understanding of the pathogenesis of RSV-induced diseases will be of considerable help in developing specific therapeutic strategies and in vaccine development.
Division of Infectious Diseases, Children's Hospital and SUNY at Buffalo, Buffalo, New York, USA.
S M
SM
van Schaik
R C
RC
Welliver
J L
JL
Kimpen
D000818:Animals; D001988:Bronchiolitis / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015289:Leukotrienes / Q000378:metabolism; D051379:Mice; D011663:Pulmonary Surfactants / Q000378:metabolism; D012135:Respiratory Sounds / Q000209:etiology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000503:physiopathology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology / Q000472:pathogenicity*
D015289:Leukotrienes; D011663:Pulmonary Surfactants