Glucocorticoid sensitivity of circulating monocytes in essential hypertension

Abstract Background Essential hypertension ranks among the strongest cardiovascular risk factors. Cytokine production by monocytes plays a key role in atherosclerosis development and acute coronary syndromes. We investigated whether stimulated monocyte cytokine release and its inhibition by glucocorticoids would differ between hypertensive and normotensive subjects. Methods Study participants were 222 middle-aged male employees with industrial jobs. Following the criteria of the World Health Organization/International Society for Hypertension, 76 subjects were classified as being hypertensive (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg). In vitro monocyte tumor necrosis factor (TNF)-α release after lipopolysaccharide (LPS) stimulation was assessed with and without coincubation with incremental doses of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting TNF-α release by 50%. Results Hypertensive subjects showed 11% higher LPS-stimulated TNF-α release than normotensive subjects (F1,181= 5.21, P = .024). In hypertensive subjects, monocyte glucocorticoid sensitivity was 21% lower than in normotensive subjects (F1,178= 4.94, P = .027), indicating that dexamethasone inhibited relatively less TNF-α release in hypertensive subjects. Results held significance when a set of classic cardiovascular risk factors was controlled for. Conclusion The findings suggest that proinflammatory activity of circulating monocytes is higher in hypertensive than in normotensive men, providing one potential pathway to explain the increased atherosclerotic risk with essential hypertension.