Th1 and Th2 Cells are Both Required in mice Eosinophil‐ and Neutrophil‐associated Asthma models

Abstract

Objective Although two distinct inflammatory subtypes of asthma have been described in patients, most of the current available animal models mimic the features of the eosinophil-mediated asthma subtype. In a previous study, we succeeded in developing models of both types of asthma in mice sensitized either orally or nasally with whole peanut protein extract in the presence of cholera toxin and further submitted to nasal challenge with the allergen. The aim of the present study was to characterize the involvement of Th1 and Th2 cytokines in these two models. Methods: The protocols of nasal or oral sensitization were tested in mice deficient in Th1 (IL-12 and IFN-g) or Th2 (IL-4 and IL-13) cytokines. Serum antibody responses to peanut sensitization and lung inflammatory responses to peanut challenge were compared in wild-type and cytokine knock-out mice. Results: Antibody responses were primarily controlled by Th2 and Th1 cytokines, in the models of eosinophil-associated and neutrophil-associated asthma, respectively. Furthermore, both Th1 and Th2 environments were required during priming for full lung reactivity in both models. Conclusion: By reproducing the features of the human diseases, these mouse models should prove useful to investigate the mechanisms involved in eosinophil- and neutrophil -associated asthma.