摘要
Imidazoquinoline compounds, such as resiquimod (R-848), are well known topically active immune modifiers that bind to toll-like receptor 7 (TLR7). The aim of this study was to characterize the R-848 induced inflammatory response in mice and to validate the response using methyl-prednisolone and anti-TNF antibody.
Intra-colonic application of R-848 to BALB/c mice induced a systemic transient elevation of TNF, CXCL1, IL-6, and IL-12p40 and a colonic elevation of cytokines/chemokines and iNOS, without infiltration of immune cells or epithelial destruction. Treatment with methyl-prednisolone or anti-TNF antibody attenuated the systemic (TNF, IL-6, IL-12p40, and CXCL1) and local (colonic TNF and iNOS mRNA expression) response induced by R-848.
In summary, intra-colonic administration of R-848 induces an acute systemic and local inflammatory response, which can be attenuated by steroids or anti-TNF antibody. We suggest that the R-848 inflammatory model can be useful in future validation of new drugs for gastrointestinal inflammatory conditions.
摘要译文
咪喹啉喹啉化合物，如瑞喹莫德（R-848）是众所周知的结合toll样受体7（TLR7）的局部活性免疫调节剂。本研究的目的是为了表征R-848诱导的小鼠炎症反应，并使用甲基泼尼松龙和抗TNF抗体来验证其反应。R-848对BALB / c小鼠的结肠内应用诱导TNF，CXCL1，IL-6和IL-12p40的系统性瞬时升高以及细胞因子/趋化因子和iNOS的结肠升高，不侵染免疫细胞或上皮破坏。用甲泼尼龙或抗TNF抗体治疗可减轻系统性（TNF，IL-6，IL-12p40，和CXCL1）和由R-848诱导的局部（结肠TNF和iNOS mRNA表达）应答。总之，R-848的结肠内给药引起急性全身和局部炎症反应，可以通过类固醇或抗TNF抗体减毒。我们建议R-848炎症模型可用于将来验证新药物的胃肠炎症状况。
Agneta Karlsson[a]; Åke Jägervall[b]; Helena Utkovic[a]; Lisa Karlsson[a]; Erika Rehnström[b]; Maria Fritsch Fredin[a]; Per-Göran Gillberg[a]; Liselotte Jansson[a]; Erik Michaëlsson[a]; Silvia Melgar[c]. Intra-colonic administration of the TLR7 agonist R-848 induces an acute local and systemic inflammation in mice[J]. Biochemical and Biophysical Research Communications, 2008,367(2): 242–248