Background: Selective inhibition of cyclooxygenase-2 (COX-2) reduces the production of prostaglandin E2 (PGE2), which can have both pro- and anti-inflammatory effects on allergic inflammation. Moreover, in vitro PGE2 has been shown to affect inflammation through the modulation of lymphocyte responses. Methods: Sixteen subjects with mild allergic asthma were recruited to a two-period cross-over study: one treatment period with the selective COX-2 inhibitor etoricoxib and one without. Each treatment period ended with an airway challenge with the patient's relevant allergen. Antigen-specific proliferation with the major cat allergen, Fel d 1, was analysed in PBMCs. CD4+ T cells were phenotyped using flow cytometry, and mRNA expression of FOXP3 in anti-CD3-stimulated CD4+ cells were analysed. Results: No significant impact of in vivo inhibition of COX-2 was detected on the proportion of Th1, Th2, or Treg cells in peripheral blood. Likewise, the treatment had minor effects on the stimulated expression of FOXP3 mRNA in CD4+ T cells. Proliferation of PBMCs to the major cat allergen Fel d 1 was slightly reduced by etoricoxib treatment in cat-allergic patients. Conclusions: Short-term treatment with the COX-2 inhibitor etoricoxib had a minor impact on T-cell responses, supporting its safe use also in subjects exposed to triggers of lymphocyte activation.

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