INVOLVEMENT OF ENDOGENOUS TUMOR-NECROSIS-FACTOR-ALPHA AND TRANSFORMING GROWTH-FACTOR-BETA DURING INDUCTION OF COLLAGEN TYPE-II ARTHRITIS IN MICE
INVOLVEMENT OF ENDOGENOUS TUMOR-NECROSIS-FACTOR-ALPHA AND TRANSFORMING GROWTH-FACTOR-BETA DURING INDUCTION OF COLLAGEN TYPE-II ARTHRITIS IN MICE
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DOI：
10.1073/pnas.89.16.7375
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发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
PALLADINO, MA
中科院分区：
文献类型：
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作者：
THORBECKE, GJ;SHAH, R;PALLADINO, MA
肿瘤坏死因子- α (tnf - α)和转化生长因子- β (tgf - β)均存在于人类和实验性关节炎啮齿动物的关节炎关节滑液中。内源性产生的tgf - β和TNF在DBA/1小鼠ii型胶原诱导关节炎（CIA）发病机制中的作用通过测定这些因素的中和单克隆抗体在疾病过程中的作用来研究。内源性和全身给药的tgf - β -1和tnf - α具有相反的作用，因为tgf - β -1和抗tnf可预防CIA，而抗tgf - β和tnf - α可增加CIA的发生率和/或严重程度。腹腔注射tgf - β -1，剂量为每天2 μ g，持续14天，即使在关节炎发展时开始注射，也能显著改善关节炎，尽管它不能逆转已建立的疾病。同时注射tgf - β -1、tnf - α或白细胞介素1- α对先前静脉注射II型胶原诱导的CIA抗性没有显著影响。由此可见，内源性TNF和tgf - β的产生在决定CIA病程中起重要作用。
Both tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) are found in synovial fluid from arthritic joints of humans and of rodents with experimental arthritis. The role of endogenously produced TGF-beta and TNF in the pathogenesis of collagen type II-induced arthritis (CIA) in DBA/1 mice was examined by determining the effect of neutralizing monoclonal antibodies to these factors on the course of the disease. Endogenously produced as well as systemically administered TGF-beta-1 and TNF-alpha had opposite effects, since TGF-beta-1 and anti-TNF protected against CIA, whereas anti-TGF-beta and TNF-alpha increased CIA incidence and/or severity. Intraperitoneally injected TGF-beta-1 at a dose of 2-mu-g per day for 14 days significantly ameliorated arthritis, even when started at the time of arthritis development, although it did not reverse established disease. The resistance to CIA induction caused by a prior intravenous injection of collagen type II was not significantly influenced by the simultaneous injection of TGF-beta-1, TNF-alpha, or interleukin 1-alpha. It is concluded that the endogenous production of TNF and TGF-beta is important in determining the course of CIA.