Comparative analysis of cytokine induction in human vascular endothelial and smooth muscle cells.

Cells of the blood vessel wall are both targets for and sources of certain cytokines. Various stimuli including bacterial lipopolysaccharides (LPS) or Interleukin 1 (IL1) induce elaboration of immunoregulatory and inflammatory mediators by human vascular endothelial cells (EC) and smooth muscle cells (SMC). We compared the capacity of EC and SMC to produce interleukin 6 (IL6) in response to LPS or its lipid A moiety. Cultured SMC release IL6 even without addition of stimuli, this basal IL6 secretion increased 2 to 4 fold in response to LPS. In contrast, unstimulated EC released little IL6, but exposure to LPS increased IL6 elaboration approximately 10 fold. Lipid A also augmented IL6 production by both EC and SMC. Radioimmunoprecipitation experiments compared de novo IL6 synthesis by EC and SMC in response to LPS, and yielded results consistent with the studies of biological activity. Unstimulated EC produced no precipitable IL6, LPS-stimulated EC released newly synthesized IL6, although to a lesser extent than did IL1-stimulated cells. SMC secreted precipitable IL6 without added stimulus and in increasing amounts following exposure to LPS or IL1. Thus EC and SMC exhibit substantial quantitative differences in IL6 synthesis and release, basally and in response to LPS. The capacity of these intrinsic vessel wall cells to secrete this important immunomodulator might contribute to local regulation of the immune or inflammatory responses.