Study of high throughput screening for inhibitors of inflammatory cytokine
- VernacularTitle:炎性细胞因子抑制剂高通量筛选方法的研究
- Author:
Li ZHANG
;
Guanhua DU
- Publication Type:Journal Article
- Keywords:
IL-1;
TNF-?;
IL-8;
lipopolysaccharide;
human blood leukocyte
- From:
Chinese Pharmacological Bulletin
2003;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM The aim of our study was to establish drug screening models which can evaluate samples' effects on cytokines related with inflammtion, capable of fast and efficient screening of anti-inflammatory lead compounds on the release of inflammtory cytokines. METHODS Heparinized human blood leukocytes was evaluated as a model to study the effects of various classes of anti-inflammatory lead compounds on cytokine release/biosynthesis from leukocytes. Human blood leukocytes was stimulated with LPS (final concentration 0.5～50 mg?L -1), with or without test drugs (diclofenac, a cytooxygenase inhibitor, nordihydroguaiaretic acid NDGA, a 5-lipoxygenase inhibitor) for 1～4 h to induce cytokine release. RESULTS Human blood leukocytes stimulated with LPS could product IL-1, IL-8 and TNF-? in a dose-dependent manner. Human blood leukocytes was stimulated with LPS(5 mg?L -1) for 4h to induce cytokine release. TNF-?, IL-1 and IL-8 time-course profiles were determined in culture media, using bioassays and ELISA. LPS-mediated release of IL-1 and TNF-? was significantly suppressed by NDGA and Diclofenac. In LPS stimulated blood, NDGA and Diclofenac inhibited the release of TNF-?(IC 50 of 149 ?mol?L -1 and 23.88 ?mol?L -1) or IL-1 (IC 50 of 222.57 ?mol?L -1 and 126 ?mol?L -1). CONCLUSION This human blood leukocytes screening system in vitro has the potential to screen new cytokine release inhibitors and sites of action of new anti-inflammatory lead compounds, and increases the screening efficiency.
