Determinants and kinetics of cytokine expression patterns in lungs of vaccinated mice challenged with respiratory syncytial virus.

The development of a successful respiratory syncytial virus (RSV) vaccine will be advanced by an improved understanding of the pathogenesis of natural disease and vaccine-enhanced illness. Using a murine model, we have examined cytokine message expression and cytokine secretion in lungs of mice primed with killed or live antigens and challenged with RSV. Stable cytokine mRNA expression was achieved if the prime-challenge interval was 2 weeks. The pattern of expression of interleukin-4 (IL-4) and interferon-7 (IFN-gamma 1 mRNA was established by day 4 after challenge and was maintained at least through day 12, and was not affected by the concentration of priming immunogen or virus challenge. An enzyme-linked immunospot assay demonstrated that CD4+ T cells were responsible for the production of IL-4, while many cell types secreted IFN-gamma. These experiments begin to define the kinetics of cytokine expression and phenotypes of cytokine-producing cells following RSV infection, supporting previous findings that suggested aberrant infiltration of CD4+ T lymphocytes and excessive IL-4 secretion may play a role in the vaccine-enhanced disease associated with RSV.