Flavonolignans Inhibit IL1-beta-Induced Cross-Talk between Blood Platelets and Leukocytes

Interleukin-1 beta (IL-1 beta)the most potent pro-inflammatory is responsible for a broad spectrum of immune and inflammatory responses, it induces T-cell and B-cell activation and consequently the synthesis of other pro-inflammatory cytokines (such as IFN-gamma and TNF). IL-1 beta induces the formation of blood platelet-leukocyte aggregates (PLAs), which suggests that IL-1 beta significantly affects the cross-talk between blood platelets and the immune response system, leading to coronary thrombosis. The aim of our study is to investigate the effect of flavonolignans (silybin, silychristin and silydianin) on the IL-1 beta-induced interaction between platelets and leukocytes, as well as on the expression and the secretion of pro-inflammatory factors. Whole blood samples were pre-incubated with commercially available flavonolignans (silybin, silychristin and silydianin) in a concentration range of 10-100 mu M (30 min, 37 degrees C). Next, samples were activated by IL-1 beta for 1 h. Blood platelet-leukocyte aggregates were detected by using the double-labeled flow cytometry (CD61/CD45). The level of produced cytokines was estimated via the ELISA immunoenzymatic method. IFN- and TNF gene expression was evaluated using Real Time PCR with TaqMan arrays. We observed that in a dose-dependent manner, silybin and silychristin inhibit the IL-1-induced formation of blood platelet-leukocyte aggregates in whole blood samples, as well as the production of pro-inflammatory cytokinesIL-2, TNF, INF-gamma, and INF-beta. Additionally, these two flavonolignans abolished the IL-1 beta-induced expression of mRNA for IFN-gamma and TNF. Our current results demonstrate that flavonolignans can be novel compounds used in the prevention of cardiovascular diseases with dual-use action as antiplatelet and anti-inflammatory agents.