Division of Rheumatology and Clinical Immunology and Department of Biochemistry, Jichi Medical University, Tochigi, Japan.
J Rheumatol. 2010 Jan;37(1):18-25. doi: 10.3899/jrheum.090492. Epub 2009 Nov 16.
To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33.
Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1beta and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting.
Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS.
IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA.
确定白细胞介素 33（IL-33）在类风湿关节炎（RA）患者血清和滑液（SF）中的水平及其临床相关性。评估来自 RA 患者的活化外周血单核细胞（PBMC）和成纤维样滑膜细胞（FLS）释放 IL-33 的能力。
采集 59 例 RA 患者、10 例感染性疾病患者和 42 例健康志愿者的血清，采集 15 例 RA 患者和 13 例骨关节炎患者的 SF 样本。用蛋白 A-琼脂糖珠去除类风湿因子后，采用夹心 ELISA 法测定 IL-33 水平。用 IL-1β和肿瘤坏死因子刺激 FLS，并用或不用化学损伤处理。用抗 CD3/CD28 抗体刺激 PBMC。用 ELISA 或免疫印迹法测定细胞培养上清液和细胞裂解物中 IL-33 的水平。
RA 患者血清 IL-33 水平显著升高，尤其是高疾病活动组与中低疾病活动组相比。15 例 RA 患者的 SF 中 IL-33 水平均升高。7 例同时测定的 RA 患者 SF 样本中的 IL-33 水平高于血清样本。受损 FLS 的培养上清液中检测到 30kDa 的 IL-33 前体，但未在活化的 PBMC 和未受损的 FLS 中检测到。
RA 患者血清和 SF 样本中 IL-33 水平升高，与疾病活动度相关。IL-33 主要在炎症关节中产生；IL-33/ST2L 信号通路可能在人类 RA 的关节炎症中发挥重要作用。
