Considerable evidence has implicated respiratory tract virus potentiation of bacterial adherence, colonization, and superinfection as a significant factor contributing to the pathogenesis of otitis media (OM). Influenza A and B viruses, adenovirus, and respiratory syncytial virus are the primary respiratory tract viruses associated with this disease. Investigations have established a dramatic increase in the development of experimental OM in chinchillas co-inoculated with influenza A virus and Streptococcus pneumoniae (Spn). The mechanism underlying this phenomenon was suggested to involve, in part, viral compromise of eustachian tube mucosal integrity and function. This study was designed to assess and compare the effect of adenovirus and influenza A virus infection on adherence, the kinetics of colonization, and invasion of the middle ear by Spn in the chinchilla model of OM. Cohorts were inoculated intranasally with adenovirus type 1 or influenza A virus, and then inoculated intranasally 7 days later with Spn 6A. All cohorts were observed over a 14-day period after challenge with Spn, and the incidence and severity of OM were assessed by several methods, including culture of the nasopharynx and middle ear effusions. The data indicated that influenza A virus promotes a significant increase in nasopharyngeal colonization by Spn, an increased incidence and severity of OM, and a sustained presence of Spn in the effusions. Adenovirus infection, however, did not enhance colonization by Spn or result in an increased incidence or severity of OM.
The trachea whole organ perfusion technique was used to study the effect of tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) on the adherence of otitis media pathogen Streptococcus pneumoniae (Spn) type 6A. Tracheas were removed from chinchillas and divided equally. One-half trachea was activated by incubation with 1-10 ng/ml of either TNF alpha or IL-1 alpha prior to the addition of Spn 6A to the organ culture perfusion chamber. Colony forming units (cfu) of Spn/millimeter trachea were determined for activated tracheas and controls. Dose response and kinetics data were generated for each cytokine. The specificity of each reaction was determined by neutralization studies with specific anti-cytokine antibodies. The data indicate that both TNF alpha and IL-1 alpha increase the adherence of Spn to the respiratory epithelium of this tubal organ and suggest a mechanism which may facilitate enhanced adherence in vivo and thereby contribute to the pathogenesis of otitis media and other upper respiratory tract diseases.
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