ORIGINAL ARTICLE Tamoxifen counteracts the allergic immune response and improves allergen-induced dermatitis in mice M. Babina 1,a , F. Kirn 1,a , D. Hoser 1 , D. Ernst 1 , W. Rohde 2 , T. Zuberbier 1 and M. Worm 1 1 Department of Dermatology and Allergy and 2 Department of Experimental Endocrinology, Charit´ e Universit ¨ atsmedizin Berlin, Berlin, Germany Clinical & Experimental Allergy Correspondence: Professor Dr Margitta Worm, Department of Dermatology and Allergy, Charit´ e Universit¨ atsmedizin Berlin, Charit´ e Campus Mitte, Chariteplatz 1, D-10117 Berlin, Germany. E-mail: margitta.worm@charite.de 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. Summary 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 1 and CD8 1 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. Keywords atopic dermatitis, Igs, sex hormones, tamoxifen, Th1/Th2 cytokines Submitted 4 April 2009; revised 15 November 2009; accepted 4 January 2010 Introduction Tamoxifen (TX) represents the prototype selective oestro- gen receptor modulator (SERM) that has been used exten- sively in the therapy of breast cancer and in chemoprevention of high-risk groups [1]. TX has addi- tionally been shown to exert immunomodulatory effects. For example, TX can directly act on B cells, antigen- presenting cells (APC), neutrophils and mast cells (MC), where it elicits complex response patterns [2–8]. Most of TX’ action is believed to be mediated by oestrogen receptors to which TX binds with a high affinity to act either in a pro- or in an anti-oestrogenic manner depend- ing on tissue context [1]; the dominance of one action vs. the other is the consequence of a delicate balance between the two oestrogen receptor species (ERa and ERb) and the equipment with co-activators and co-repressors that form the multi-subunit complexes on the genes in question [1]. In addition, TX can also act in a rapid, non-genomic manner by mechanisms not related to ER signalling or via cell surface ER receptors, resulting in a plethora of changes, including the inhibition of protein kinase C, calmodulin-dependent cAMP phosphodiesterase and ion channels, respectively [8–10]. Experimental Models of Allergic Disease a The authors contributed equally. doi: 10.1111/j.1365-2222.2010.03472.x Clinical & Experimental Allergy, 40, 1256–1265  c 2010 Blackwell Publishing Ltd