The genesis of rheumatoid arthritis (RA) is complex and dependent on genetic background and exposure to environmental xenobiotic. Indeed, smoking is associated to developing and worsening pre-existing RA. Nevertheless, the mechanisms and cigarette compounds involved in the harmful processes have not been elucidated. Here, we investigated if the exposure to hydroquinone (HQ), an abundant pro-oxidative compound of cigarette and benzene metabolite, could worsen the ongoing RA. Hence, collagen-induced arthritis (CIA) was induced in male Wistar rats by s.c. injection of 400 μg (200 μL) of bovine collagen type II emulsified in complete Freund's adjuvant on day 1, and a booster injection was performed on day 7. Exposures to nebulized HQ (25 ppm), saline solution or HQ vehicle solution (5% ethanol in saline) were carried out for 1 h, once a day, on days 21–27 after CIA induction. On day 27, animals were euthanized and samples were collected for further analyses. Exposure to HQ caused loss of weight, intensified paw edema, enhanced levels of tumor necrosis factor-α (TNF-α) and anti-citrullinated protein antibody (ACPA) in the serum; augmented synoviocyte proliferation and influx of aril hydrocarbon receptor (AhR) positive cells into the synovial membrane, altered collagen fibre rearrangement in the synovia, and synoviocytes isolated from HQ exposed rats secreted higher levels of pro-inflammatory cytokines, TNF-α and interleukin-1β. Associated, we point out HQ as an environmental pollutant that aggravates RA, suggesting its participation on worsening RA in smoking patients.

类风湿关节炎（RA）的发生很复杂，并且取决于遗传背景和环境异源生物的暴露。确实，吸烟与RA的发展和恶化有关。然而，尚未阐明有害过程中涉及的机制和香烟化合物。在这里，我们调查了暴露于对苯二酚（HQ）（一种富含香烟和苯代谢物的促氧化化合物）是否会恶化正在进行的RA。因此，男性Wistar会诱发胶原蛋白诱发的关节炎（CIA）在第1天通过皮下注射在完全弗氏佐剂中乳化的400μg（200μL）II型牛胶原蛋白在大鼠中进行注射，并在第7天进行加强注射。 （在CIA诱导后的第21-27天）每天一次（含5％乙醇的生理盐水）进行1小时。在第27天，对动物实施安乐死并收集样品以进行进一步分析。暴露于HQ会导致体重减轻，爪水肿加剧，血清中的肿瘤坏死因子-α（TNF-α）和抗瓜氨酸化蛋白抗体（ACPA）水平升高；滑膜细胞增殖增加，假种皮碳氢化合物受体（AhR）阳性细胞流入滑膜，改变滑膜中胶原纤维的重排，从暴露于HQ的大鼠中分离出的滑膜细胞分泌更高水平的促炎细胞因子，TNF-α和白介素-1β。与此相关的是，我们指出HQ是加重RA的一种环境污染物，表明其参与吸烟患者的RA恶化。