Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells

The catecholamine-mediated modulation of the cytokine network has primarily been demonstrated for leukocytes, Whereas catecholamines decrease the LPS- induced production of IL-6 by leukocytes, serum levels of IL-6 are dramatic ally increased by the catecholamine epinephrine in animal endotoxemia model s. We now demonstrate that epinephrine as well as norepinephrine can induce IL-6 in an endothelial cell line (HMEC-1). Furthermore, these catecholamin es could even potentiate the LPS-induced IL-5 protein production. The syner gistic effect of catecholamines and LPS could be reproduced in primary huma n skin microvascular endothelial cells. The catecholamine-induced IL-6 stim ulation is based on increased IL-6 mRNA levels. RNA stability assays reveal ed that this regulation is not a result of enhanced RNA stability and there fore is most likely due to an increased transcription. Treatment with cyclo heximide indicated that new protein synthesis is not necessary for this tra nscriptional up-regulation of IL-6 mRNA Preincubation with alpha and beta r eceptor antagonists showed that the effect is mediated by beta(1)- and beta (2)-adrenergic receptors. Thus, endothelial cells might be a possible sourc e of increased IL-6 production observed in situations such as stress or sep tic shock, in which catecholamines are elevated due to endogenous productio n or exogenous application.-Gonlikiewicz, A., Sautner, T., Brostjan, C., Sc hmierer, B., Fugger, R., Roth, E., Muhlbacher, F., Bergmann, M. Catecholami nes up-regulate lipopolysaccharide-induced IL-6 production in human microva scular endothelial cells.