Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease.
Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease.
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DOI：
10.1186/ar318
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Hamilton JA
中科院分区：
文献类型：
--
作者：
Cook AD;Braine EL;Campbell IK;Rich MJ;Hamilton JA
越来越多的证据表明，生长因子粒细胞-巨噬细胞集落刺激因子(GM-CSF)在包括关节炎在内的炎症性疾病中发挥了作用。在本研究中，我们观察了抗GM-CSF中和单抗治疗胶原性关节炎(CIA)的有效性。免疫DBA/1小鼠建立CIA模型，在不同时间、不同剂量用中和抗GM-CSF单抗或同型对照单抗进行治疗。在关节炎发作之前，在抗原攻击时，抗GM-CSF单抗治疗在改善随后的疾病方面是有效的。关节炎的调节主要被认为是总体疾病严重程度的降低，无论是每只小鼠受影响的肢体数量还是受影响肢体的临床评分。重要的是，抗GM-CSF单抗治疗改善了现有的疾病，这既被视为减少了最初受影响的肢体的进展数量，也减少了受影响的额外肢体的数量。组织学观察，抗GM-CSF组炎症反应减轻，软骨破坏减轻，肿瘤坏死因子-a、IL-1、IL-1、IL在这些小鼠的关节组织清洗中也减少了。然而，抗GM-CSF单抗治疗对II型胶原的体液免疫和细胞免疫均无影响。这些结果表明，GM-CSF在CIA中的主要作用是介导II型胶原炎症反应的效应期。结果还强调了GM-CSF在CIA炎症和关节炎的持续发展中的重要作用，可能对类风湿性关节炎具有治疗意义。
There is mounting evidence for a role of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in inflammatory disease, including arthritis. In the present study, we examined the effectiveness of treatment of collagen-induced arthritis (CIA) with a neutralizing mAb to GM-CSF. DBA/1 mice were immunized for the development of CIA and treated at different times, and with different doses, with neutralizing mAb to GM-CSF or isotype control mAb. Anti-GM-CSF mAb treatment prior to the onset of arthritis, at the time of antigen challenge, was effective at ameliorating the ensuing disease. Modulation of arthritis was seen predominantly as a reduction in overall disease severity, both in terms of the number of limbs affected per mouse and the clinical score of affected limbs. Importantly, anti-GM-CSF mAb treatment ameliorated existing disease, seen both as a reduction in the number of initially affected limbs progressing and lower numbers of additional limbs becoming affected. By histology, both inflammation and cartilage destruction were reduced in anti-GM-CSF-treated mice, and the levels of tumor necrosis factor-a and IL-1? were also reduced in joint tissue washouts of these mice. Neither humoral nor cellular immunity to type II collagen, however, was affected by anti-GM-CSF mAb treatment. These results suggest that the major effect of GM-CSF in CIA is on mediating the effector phase of the inflammatory reaction to type II collagen. The results also highlight the essential role of GM-CSF in the ongoing development of inflammation and arthritis in CIA, with possible therapeutic implications for rheumatoid arthritis.
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影响因子：
3.8
作者：
BRISSETTE, WH;BAKER, DA;GRIFFITHS, RJ
通讯作者：
GRIFFITHS, RJ
影响因子：
20.3
作者：
Metcalf, D;Robb, L;DiRago, L
通讯作者：
DiRago, L
影响因子：
5.6
作者：
HAMILTON, JA;STANLEY, ER;SHADDUCK, RK
通讯作者：
SHADDUCK, RK
慢性炎性关节炎中的细胞因子。 iv。粒细胞/巨噬细胞刺激因子介导的II类MHC抗原对人单核细胞的诱导：类风湿关节炎中的可能作用。
影响因子：
15.3
作者：
Alvaro-Gracia, J M;Zvaifler, N J;Firestein, G S
通讯作者：
Firestein, G S
DOI：
10.1073/pnas.89.20.9784
发表时间：
1992-10-15
影响因子：
11.1
作者：
WILLIAMS, RO;FELDMANN, M;MAINI, RN
通讯作者：
MAINI, RN