Supplementary Material for: Selective COX-2 Inhibition Exerts No Negative Effects on Peripheral Blood Lymphocytes in Allergic Asthmatics

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.

研究背景：选择性抑制环氧合酶-2（cyclooxygenase-2, COX-2）可减少前列腺素E2（prostaglandin E2, PGE2）的生成，而PGE2对过敏性炎症兼具促炎与抗炎双重作用。此外，体外（in vitro）研究已证实PGE2可通过调控淋巴细胞反应影响炎症进程。
研究方法：本研究纳入16例轻度过敏性哮喘受试者，采用两周期交叉试验设计：一组接受选择性COX-2抑制剂依托考昔（selective COX-2 inhibitor etoricoxib）治疗，另一组不接受该治疗。每个治疗周期结束后，均对受试者进行其致敏特异性变应原的气道激发试验。对外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）中猫主要变应原Fel d 1诱导的抗原特异性增殖水平进行分析。采用流式细胞术（flow cytometry）对CD4+T细胞进行表型鉴定，并对抗CD3刺激的CD4+细胞中FOXP3的mRNA表达水平进行检测。
研究结果：体内（in vivo）抑制COX-2未对外周血中Th1、Th2及Treg细胞的比例产生显著影响。同样，该治疗对CD4+T细胞中经刺激后的FOXP3 mRNA表达水平仅存在微弱影响。猫过敏性哮喘患者的PBMCs经主要猫变应原Fel d 1刺激后的增殖水平，经依托考昔治疗后出现轻微降低。
研究结论：短期使用COX-2抑制剂依托考昔对T细胞反应仅存在微弱影响，该结果支持其在淋巴细胞活化触发因素暴露人群中的安全应用。