Glycoprotein IIb/Iiia Antagonist Could Reduce the Inflammatory Factors IL-6, IL-1β, TNF-α of Atherosclerosis Rabbits in Vivo

Background: Glycoprotein (GP) IIb/IIIa antagonists have been widely used in clinical practice. It had been demonstrated that although GPIIb/IIIa antagonists could reduce 30%~ 50% ischemic events around coronary artery intervention therapy, it had only limited effects on the long term survival. We want to explore the effects of GPIIb/IIIa antagonists besides inhibiting platelet aggregation. So we observed the effects of tirofiban (a GP IIb/IIIa antagonist) in vivo.

Design: the atherosclerosis model rabbits were divided into 4 groups. Each group got a 1.7ml/h nature saline (control group), 3.125mg/L, 12.5 mg/L or 50mg/L tirofiban continuous intravenous injection for 48 hours respectively. Platelet aggregation maximum (PAG(M)), plasma interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α were measured at 0 hour, 12th hour, 24th hour and 48th hour time point.

Results: In vivo, compare to the value at 0 hour, the PAG(M) didn’t change significantly at the 12th hour, 24th hour and 48th hour time point in the control group and 3.125mg/L tirofiban group. While the PAG(M) was reduced at the 12th hour, 24th hour and 48th hour time point in the 12.5mg/L and 3.125mg/L tirofiban group. About the inflammatory factors, in control group, compare to the index at 0 hour, plasma IL-1β, IL-6 and TNF-α concentration were all increased significantly at the 12th hour time point. In the 3.125mg/L tirofiban group, the plasma IL-1β and IL-6 concentration elevated significantly at the 24th hour time point. In the 12.5mg/L tirofiban group, the plasma IL-6 and TNF-α concentration at 24th hour time point, the plasma IL-1β, IL-6 and TNF-α concentration at 48th hour time point were all decreased significantly. In 50mg/L tirofiban group, the plasma IL-6 concentration at 12th hour time point, the plasma IL-1β, IL-6 and TNF-α concentration at 24th hour and 48th hour time point were all decreased. At 0 hour, plasma IL-1β, IL-6 and TNF-α concentration had no difference among the 4 groups (IL-1β P_ANOVA=0.954, IL-6 P_ANOVA=0.954, TNF-α P_ANOVA=0.954. n=5). While at 12 hour, 24 hour or 48 hour time points, among the 4 groups, the index value of the IL-1β, IL-6 and TNF-α decreased along with the increase of the tirofiban concentration (P_ANOVA<0.01. n=5).

Conclusion: In vivo, full dosage tirofiban could inhibit PAG(M), decrease the production of rabbit plasma IL-6, IL-1β and TNF-α. While little dosage tirofiban (≤3.125mg/L) had no effect on PAG(M), could not decrease the production of rabbit plasma IL-6, IL-1β and TNF-α. GP IIb/IIIa antagonist could reduce the inflammatory factors in full dosage.