Effects of in vitro treatment with fluticasone propionate on natural killer and lymphokine-induced killer activity in asthmatic and healthy individuals

BACKGROUND: Topical corticosteroids are beneficial in the treatment of allergic respiratory disorders; they exert effects on a number of cells involved in allergic inflammatory reactions. On the other hand, major histocompatibility complex (MHC)-unrestricted cytotoxicity (i.e., natural killer [NK] cell activity) may play a role in the inflammatory allergic reaction. The objective was to gain insight into the mechanisms of the therapeutic effects of fluticasone propionate (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore, we evaluated the NK and lymphokine-activated killer (LAK) activity of effector cells in vitro treated or not with FP. METHODS: Evaluations were made on peripheral blood mononuclear cells (PBMNCs), obtained from healthy volunteers (n = 10) and from asthmatic atopic subjects (n = 10) with allergy to Parietaria. RESULTS: Asthmatic patients had significantly increased NK activity (P= 0.0008), and interleukin (IL)-2- (P=0.0005) and interferon (IFN)-alpha-induced LAK activities (P=0.0005). In both groups, FP 10(-7) M significantly reduced NK activity (P<0.0001), IL-2-induced LAK activity (P<0.0001), and IFN-alpha-induced LAK activity (P<0.0001). Similar results were obtained with FP 10(-8) M. CONCLUSIONS: Since MHC-unrestricted cytotoxicity has been implicated in the development of allergen-induced eosinophilic airway inflammation, inhibition of NK and LAK activity by FP may contribute to the steroid therapeutic effect in asthma.