The promoting effect of epinephrine on lipopolysaccharideinduced interleukin-8 production in whole blood may be mediated by thromboxane A 2

Abstract

Epinephrine is known to enhance lipopolysaccharide (LPS)-induced interleukin (IL)-8 secretion in a platelet dependent manner. To determine whether thromboxane A 2 (TxA 2; a product from activated platelets) is involved in this process, blood samples drawn either before or 2 h after oral administration of 440 mg acetylsalicylic acid (ASA) were stimulated with LPS (5 ngmL -1) and different concentrations of epinephrine were added (0.1-100.0 mmol L -1). ASA ingestion significantly (global P<0.05) reduced the enhancing effect of epinephrine on LPS-induced IL-8 release by 15-28%. To further explore whether TxA 2 may be involved in this process, a TxA 2 agonist (U46619) was added to whole blood together with LPS instead of epinephrine. U46619 mimicked the epinephrine effect: 20 ngmL -1 U46619 enhanced LPS-induced IL-8 release by 39% (P<0.05). Furthermore, preincubation of whole blood with 75 mmol L -1 or 150 mmol L -1 SQ29548, a TxA 2 receptor antagonist, completely blocked epinephrine's promoting effect on LPS-induced IL-8 release. Since thrombin-activated platelets have been reported to be important in the production of IL-8 in monocytes through the activation of monocytes by exposed RANTES in a P-selectin-dependent reaction, we suggest that the epinephrine effect is mediated by enhanced TxA 2 production and subsequent rise in the exposure of RANTES and P-selectin on the platelets of whole blood. © 2003 International Society on Thrombosis and Haemostasis.