Schuerwegh A J, De Clerck L S, De Schutter L, Bridts C H, Verbruggen A, Stevens W J
Department of Immunology, Allergology and Rheumatology, University of Antwerp, UIA, Antwerp, Belgium.
Cytokine. 1999 Oct;11(10):783-8. doi: 10.1006/cyto.1998.0483.
Type 1 cytokines (a.o. IL-2 and IFN-gamma) play an important role in the pathogenesis of rheumatoid arthritis. On the other hand, IgE-mediated diseases such as allergic asthma and atopic dermatitis show a type 2 cytokine (amongst others IL-4 and IL-5) profile. This study examined simultaneously the intracellular production of IL-2, IFN-gamma, IL-4 and IL-5 in T-lymphocytes of patients with rheumatoid arthritis during treatment with methotrexate or salazopyrin, patients with allergic asthma or atopic dermatitis under stable treatment, compared to healthy controls.A three-colour flow cytometric analysis was used for cytokine detection in T-helper cells and T-suppressor/cytotoxic cells. Compared to controls, patients with symptomatic atopic dermatitis showed an increased number of IL-4-producing T-helper lymphocytes in basal circumstances (P=0.001), in contrast to asymptomatic allergic asthma patients. Compared to controls, rheumatoid arthritis patients, treated with salazopyrin, showed an increased number of IL-2-producing T-helper and T-suppressor/cytotoxic lymphocytes after in vitro stimulation with PMA and ionomycin (P=0.01). In contrast, rheumatoid arthritis patients, treated with methotrexate, a more potent disease modifying drug, did not show this type 1 cytokine profile. A positive correlation was found between the number of IFN-gamma producing T-helper cells and disease activity (Ritchie Index and number of swollen joints) in both rheumatoid arthritis patient groups. Active atopic dermatitis patients showed a type 2 cytokine profile, whereas stable asthma patients with lower disease activity did not show a predominance of type 2 cytokines. Rheumatoid arthritis patients under treatment with salazopyrin had a type 1 cytokine profile, which could not be demonstrated in patients treated with methotrexate. This imbalance between type 1 and type 2 cytokines in different immune mediated disorders can be related with treatment and the grade of disease activity. These results stress the need for further investigation of the influence of therapy on cytokine profiles.
1型细胞因子(如白细胞介素-2和干扰素-γ)在类风湿性关节炎的发病机制中起重要作用。另一方面,如过敏性哮喘和特应性皮炎等IgE介导的疾病表现出2型细胞因子(包括白细胞介素-4和白细胞介素-5)特征。本研究同时检测了类风湿性关节炎患者在接受甲氨蝶呤或柳氮磺胺吡啶治疗期间、稳定期治疗的过敏性哮喘或特应性皮炎患者以及健康对照者的T淋巴细胞中白细胞介素-2、干扰素-γ、白细胞介素-4和白细胞介素-5的细胞内产生情况。采用三色流式细胞术分析检测辅助性T细胞和抑制性/细胞毒性T细胞中的细胞因子。与对照组相比,有症状的特应性皮炎患者在基础情况下产生白细胞介素-4的辅助性T淋巴细胞数量增加(P = 0.001),无症状的过敏性哮喘患者则相反。与对照组相比,接受柳氮磺胺吡啶治疗的类风湿性关节炎患者在经佛波酯和离子霉素体外刺激后,产生白细胞介素-2的辅助性T细胞和抑制性/细胞毒性T淋巴细胞数量增加(P = 0.01)。相比之下,接受更有效的病情缓解药物甲氨蝶呤治疗的类风湿性关节炎患者未表现出这种1型细胞因子特征。在两个类风湿性关节炎患者组中,产生干扰素-γ的辅助性T细胞数量与疾病活动度(里奇指数和关节肿胀数量)之间存在正相关。活动期特应性皮炎患者表现出2型细胞因子特征,而疾病活动度较低的稳定期哮喘患者未表现出2型细胞因子优势。接受柳氮磺胺吡啶治疗的类风湿性关节炎患者具有1型细胞因子特征,而接受甲氨蝶呤治疗的患者未表现出这一特征。不同免疫介导疾病中1型和2型细胞因子之间的这种失衡可能与治疗及疾病活动度等级有关。这些结果强调需要进一步研究治疗对细胞因子谱的影响。