Szekanecz Z, Halloran M M, Volin M V, Woods J M, Strieter R M, Kenneth Haines G, Kunkel S L, Burdick M D, Koch A E
Northwestern University Medical School, Chicago, Illinois 60611, USA.
Arthritis Rheum. 2000 Jun;43(6):1266-77. doi: 10.1002/1529-0131(200006)43:6<1266::AID-ANR9>3.0.CO;2-P.
To examine cytokine and chemokine production during the evolution of rat adjuvant-induced arthritis (AIA), a model of rheumatoid arthritis.
Clinical and laboratory assessment of the course of AIA was performed over a 47-day period. Levels of the cytokines tumor necrosis factor a (TNFalpha), interleukin-1beta (IL-1beta), and IL-6, as well as levels of the chemokines macrophage inflammatory protein 1alpha (MIP-1alpha) and JE, the murine homolog of monocyte chemoattractant protein 1, were determined by enzyme-linked immunosorbent assay in the sera and joints of AIA and control rats. Synovia from AIA rats were (immuno)histochemically analyzed. Results of cytokine and chemokine measurements were correlated with clinical and laboratory markers of inflammation and histology.
Early (before day 14 post adjuvant injection) and later phases of AIA could be distinguished. Cytokine and chemokine production was increased in AIA versus control rats. The production of TNFalpha, IL-1beta, MIP-1alpha, and, as determined earlier, epithelial neutrophil-activating peptide 78-like protein was abundant prior to and during the course of AIA, while that of IL-6 and JE was elevated in the late phase of AIA. Cytokine and chemokine levels were correlated with the clinical symptoms of arthritis and blood neutrophil counts. Joint levels of IL-1beta showed correlation with synovial lining proliferation and neutrophil ingress into AIA synovium.
Cytokines and chemokines are involved in the clinical, laboratory, and histologic changes underlying AIA. The production of these mediators may be temporally and spatially regulated. These findings may be important for the optimal timing of cytokine and chemokine targeting.
研究大鼠佐剂性关节炎（AIA）（一种类风湿性关节炎模型）病程中细胞因子和趋化因子的产生情况。
在47天的时间里对AIA病程进行临床和实验室评估。通过酶联免疫吸附测定法测定AIA大鼠和对照大鼠血清及关节中细胞因子肿瘤坏死因子α（TNFα）、白细胞介素-1β（IL-1β）和IL-6的水平，以及趋化因子巨噬细胞炎性蛋白1α（MIP-1α）和JE（单核细胞趋化蛋白1的小鼠同源物）的水平。对AIA大鼠的滑膜进行（免疫）组织化学分析。细胞因子和趋化因子测量结果与炎症和组织学的临床及实验室指标相关。
可区分AIA的早期（佐剂注射后14天前）和后期阶段。与对照大鼠相比，AIA大鼠中细胞因子和趋化因子的产生增加。在AIA之前及病程中，TNFα、IL-1β、MIP-1α以及先前测定的上皮中性粒细胞激活肽78样蛋白的产生丰富，而IL-6和JE在AIA后期升高。细胞因子和趋化因子水平与关节炎的临床症状和血液中性粒细胞计数相关。关节中IL-1β水平与滑膜衬里增生以及中性粒细胞进入AIA滑膜相关。
细胞因子和趋化因子参与AIA潜在的临床、实验室和组织学变化。这些介质的产生可能在时间和空间上受到调节。这些发现对于细胞因子和趋化因子靶向治疗的最佳时机可能很重要。
