Tamoxifen counteracts the allergic immune response and improves allergen-induced dermatitis in mice

P>Background Tamoxifen (TX) represents the prototype selective oestrogen receptor modulator. In addition to its use in breast cancer, TX possesses immunomodulatory functions and displays beneficial effects in models of systemic lupus erythematosus. We hypothesized that TX might inhibit type I allergic reactions, which are also characterized by deviations in humoral immunity. Objective To evaluate the effects of TX on the allergic immune response in appropriate mouse models. Methods Balb/c mice were sensitized with ovalbumin (OVA)-alum by the intraperitoneal route, and humoral parameters, T cell cytokine patterns and OVA-induced ear swelling responses were determined in a preventive (start of TX treatment before sensitization) and a therapeutic setting (start after sensitization), respectively. In addition, the impact of TX on clinical signs, epidermal thickness and leucocyte infiltration of the skin was investigated in a model of allergen-induced dermatitis. Results Preventive TX treatment interfered with all aspects of the allergic immune response, leading to a reduction of allergen-specific Ig levels (IgE, IgG1 and IgG2a), a skewing effect in the T cell compartment with the inhibition of IL-4 and an abrogation of ear swelling responses. Interestingly, a therapeutic TX administration was also effective in reducing Ig levels and ear swelling responses. The vigorous systemic effects were additionally mirrored by local changes in allergen-dependent dermatitis with reduced clinical symptoms, diminished epidermal thickness and decreased CD4+ and CD8+ cell infiltrates. Conclusion TX inhibits allergic responses when given preventively and also therapeutically, and improves allergen-induced dermatitis. Because of its effectiveness, TX could bear significant therapeutic potential for the treatment of allergies. Cite this as: M. Babina, F. Kirn, D. Hoser, D. Ernst, W. Rohde, T. Zuberbier and M. Worm, Clinical & Experimental Allergy, 2010 (40) 1256-1265.