Introduction: In both asthma and rhinitis, a proportion of patients are skin-test negative. It is possible that an native recognition of common inhalant allergens by epithelial cells resulting in local inflammatory processes may contribute to the pathogenesis of the so-called non-allergic asthma and non-allergic rhinitis. In the present study we focused on the ability of inhalant allergens to induce the release of pro-inflammatory cytokines and cell detachment in human pulmonary epithelial cell lines and primary nasal epithelial cells from non-atopic individuals.Materials and Methods: Cultures of A549 and NCl-H292 cells and primary nasal epithelial cells from non-atopic individuals were incubated with Lepidoglyphus destructor, Dermatophagoides pteronyssinus, Timothy grass (Phleum pratensis) and Birch (Betula verrucosa) pollen extracts. The production of IL-8, IL-6, MCP-1 and GM-CSF in culture supernatants was quantified. Gel filtration chromatography was used to fractionate the extracts.Results: It was shown that all four extracts are able to induce a cytokine response in the epithelial cells studied. In addition to the ability to induce cell detachment, the mite extracts were able to elicit a cytokine response in a dose-dependent fashion. Both cell detachment and cytokine production was highly dependent on the proteolytic enzyme activities in the mite extracts. In spite of the lack of proteolytic enzym activity, the pollen extract were able to induce a cytokine response but not cell detachment in the epithelial cell cultures tested.Conclusion: These preliminary results reinforce the hypothesis that allergens may induce airways inflammation by means other than their antigenic activity.