Leech M, Metz C, Santos L, Peng T, Holdsworth S R, Bucala R, Morand E F
Monash Medical Centre, Clayton, Melbourne, Australia.
Arthritis Rheum. 1998 May;41(5):910-7. doi: 10.1002/1529-0131(199805)41:5<910::AID-ART19>3.0.CO;2-E.
Recent studies have established an essential role for macrophage migration inhibitory factor (MIF) in T cell and macrophage activation, both of which are characteristics of rat adjuvant arthritis. This study investigated the role of MIF in early adjuvant arthritis.
MIF was detected in rat synovium by immunohistochemistry and enzyme-linked immunosorbent assay using specific monoclonal antibodies (MAb). Anti-MIF MAb treatment was administered, and the effects on clinical aspects of adjuvant arthritis were assessed.
MIF was absent from normal rat synovium prior to adjuvant injection, but was detectable on day 4 after injection (6 days before the onset of clinical disease) and was colocalized with ED-1+ macrophages throughout the evolution of the disease. Levels of MIF were increased in established adjuvant arthritis sera, and adjuvant arthritis synovial macrophages released MIF at a mean +/- SEM concentration of 607.9 +/- 201.5 pg/ml. Anti-MIF treatment led to profound, dose-dependent inhibition of the adjuvant arthritis clinical score, paw swelling, and synovial lavage leukocyte numbers (P < 0.001), and also resulted in reduced synovial macrophage and T cell accumulation.
These findings demonstrate an important role for MIF in the evolution of rat adjuvant arthritis.
近期研究已证实巨噬细胞移动抑制因子（MIF）在T细胞和巨噬细胞激活过程中起关键作用，而这两者均为大鼠佐剂性关节炎的特征。本研究旨在探讨MIF在早期佐剂性关节炎中的作用。
采用特异性单克隆抗体（MAb），通过免疫组织化学和酶联免疫吸附测定法在大鼠滑膜中检测MIF。给予抗MIF MAb治疗，并评估其对佐剂性关节炎临床症状的影响。
在注射佐剂前，正常大鼠滑膜中未检测到MIF，但在注射后第4天（临床疾病发作前6天）可检测到，且在疾病发展过程中与ED-1+巨噬细胞共定位。在已确诊的佐剂性关节炎血清中，MIF水平升高，佐剂性关节炎滑膜巨噬细胞释放MIF的平均浓度为607.9±201.5 pg/ml（±标准误）。抗MIF治疗导致佐剂性关节炎临床评分、 paw肿胀和滑膜灌洗白细胞数量受到显著的、剂量依赖性抑制（P<0.001），同时也减少了滑膜巨噬细胞和T细胞的积聚。
这些发现表明MIF在大鼠佐剂性关节炎的发展中起重要作用。
