Cate cholamines induce aggravation of aortic and coronary atherosclerosis in monkeys inhibitor and play a direct role in atherogenesis and cardiovascular disease. Epinephrine and norepinephrine increase the uptake of low density lipoprotein in atheroscelotic plaques in rab bits and rats as well as enhance proliferation of rat endothelial and smooth muscle cells. It has been reported that norepinephrine increases adherence and chemotaxis of macrophages. Epinephrine also upreg ulates the surface expression of L selectin on monocytes in vitro. Most recently, we have reported that nitric oxide production from macrophages induced by LPS is enhanced by catecholamines. Both epinephrine and IL 1 are involved in acute phase responses seen in stress and in coronary artery disease.

Studies have shown that norepinephrine can induce IL 1 mRNA in mycocardial tissue and that infusion of IL 1 in animal models can induce expression of catecholamines. These data suggest that, in some conditions, both IL 1 and cat echolamines can be delivered to tissues that can then mediate additive or modulatory effects. Moreover, as reviewed by Gidron Y et al, stress in conjunction with the release of catecholamines and proinflammatory cytokines, can potentiate atherogenesis. Hence, studies of the interactions between catecholamines, monokines and inflammatory cell activation are especially relevant. The aim of the study was to determine whether epinephrine affects IL 1 induced proatherogenic cytokine production in mast cells, a phenomenon previously not described.

Our results indicated that epinephrine synergized with IL 1 in the production of proatherogenic cytokines, suggest ing a potential role for this interaction in inflammatory and atherogenic states. Results Epinephrine enhances IL 1 induced IL 6, IL 8, and IL 13 production in mast cells Human mast cell line, HMC 1, was incubated with IL 1 at various concentrations for 24 hours. The cell free super natants of the cultures were harvested and subjected to IL 6 assay. HMC 1 cultured in medium alone produced trace amounts of IL 6. The IL 6 production from HMC 1 cultures treated with IL 1 was significantly increased in a dose dependent manner. Since there was no significant difference in the IL 6 production induced by IL 1 at concentrations of 10 and 50 ng ml, 10 ng ml of IL 1 has been used to induce cytokine produc tion in HMC 1 for the rest of the experiments.

Epine phrine alone at a concentration of 10 3 M did not induce production of IL 6 in HMC 1. When epine phrine at 10 3 to 10 7 M concentration was added simulta ing gene was calculated and assigned Drug_discovery as the intensity index. The intensity indices for IL 6 were 0. 36 for the con trol, 0. 39 for IL 1 alone, 0. 33 for epinephrine alone, and 0. 54 for IL 1 plus epinephrine. IL 1 activated IL 8 mRNA production but epinephrine had no effect on IL 8 transcripts.