Monocyte-derived interleukin 1: effects on norepinephrine-stimulated aortic contraction and phosphoinositide turnover

Medium conditioned by silica-stimulated human peripheral blood monocytes expresses vascular suppressive activity. Rat aortic rings, after incubation in conditioned medium, exhibited comprised contraction to stimulation by norepinephrine (NE). Maximal contraction (300 +/- 51 mg tension/mg tissue) and sensitivity (-5.91 +/- 0.23 M [log EC50]) were both reduced in comparison to contraction (762 +/- 66) and sensitivity (-7.42 +/- 0.11) displayed by rings after incubation in control medium. A polyvalent antibody (Ab) against human interleukin 1 (Il-1) neutralized the suppressive activity in conditioned medium. Rings incubated in conditioned medium containing Ab exhibited normal maximal contraction (722 +/- 46) and a partial restoration of sensitivity to NE (-6.91 +/- 0.13). In contrast, incubation of rings in control medium supplemented with recombinant human Il-1 resulted in a dose-dependent suppression of aortic contraction to NE that was analogous to the defects induced by monocyte-conditioned medium. No significant differences in NE-stimulated phosphoinositide hydrolysis were present between rings incubated in Ab-treated or untreated conditioned or control media. The data suggest that monocyte-derived Il-1 may have a significant influence on vascular contractile function and that the mechanism by which Il-1 induces vascular dysfunction cannot be demonstrated to involve inhibition of NE-stimulated phosphoinositide metabolism.