Choo-Kang Brian S W, Hutchison Sharon, Nickdel Mohammad B, Bundick Robert V, Leishman Andrew J, Brewer James M, McInnes Iain B, Garside Paul
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, Scotland, UK.
Trends Immunol. 2005 Oct;26(10):518-22. doi: 10.1016/j.it.2005.07.007.
Despite expanding use of drugs blocking tumour necrosis factor (TNF), their precise mechanisms of action remain unclear. Early assumptions that they act by direct neutralization of the toxic inflammatory effects of TNF might be too simplistic because they explain neither the range of effects observed nor the varying properties of different TNF-blocking agents. Recent studies have demonstrated a key role for mast cell-derived TNF in the increase in lymph node size and the organizational complexity that accompanies a developing immune response. Regulation of this phenomenon might comprise a novel mode of action for TNF-directed therapy: by preventing this lymph node hyperplasia, TNF blockade could modulate immune responses, ameliorating pathology in autoimmune diseases, such as rheumatoid arthritis.
尽管阻断肿瘤坏死因子（TNF）的药物使用越来越广泛，但其确切作用机制仍不清楚。早期认为它们通过直接中和TNF的毒性炎症作用而起作用的假设可能过于简单，因为这既无法解释观察到的效应范围，也无法解释不同TNF阻断剂的不同特性。最近的研究表明，肥大细胞衍生的TNF在淋巴结肿大以及伴随免疫反应发展的组织复杂性增加中起关键作用。对这一现象的调节可能构成TNF导向治疗的一种新作用模式：通过预防这种淋巴结增生，TNF阻断可以调节免疫反应，改善自身免疫性疾病（如类风湿性关节炎）中的病理状况。
