CARDIOVASCULAR MEDICINE

Monocyte proinflammatory cytokine release is higher and glucocorticoid sensitivity is lower in middle aged men than in women independent of cardiovascular risk factors

P H Wirtz¹, R von Känel², N Rohleder³, J E Fischer⁴

¹ Institute of Clinical Psychology II, University of Zurich, Zurich, Switzerland
² Division of Psychosomatic Medicine, Department of Internal Medicine, University Hospital, Barne, Switzerland
³ Institute of Biopsychology, Technical University, Dresden, Germany
⁴ Institute for Behavioural Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland

Correspondence to:
Correspondence to:
Dr Joachim E Fischer
Institute of Behavioural Sciences, Swiss Federal Institute of Technology, Turnerstrasse 1, CH-8092 Zurich, Switzerland; fischer{at}ifv.gess.ethz.ch

Objective: To investigate whether stimulated monocyte cytokine release and its inhibition by glucocorticoids differs between men and women.

Design: In vitro monocyte interleukin 6 (IL-6) and tumour necrosis factor (TNF) release after lipopolysaccharide stimulation were assessed with and without co-incubation with increasing doses of dexamethasone and hydrocortisone separately. Glucocorticoid sensitivity was defined as the amount of a particular glucocorticoid required to inhibit lipopolysaccharide stimulated monocyte cytokine release by 50%. The established cardiovascular risk factors of age, body mass index, number of cigarettes smoked daily, low density cholesterol to high density cholesterol ratio, systolic and diastolic blood pressure, and haemoglobin A1c were used as covariates.

Setting: Aircraft manufacturing plant in southern Germany.

Patients: 269 middle aged male and 36 middle aged female employees.

Results: Release of monocyte IL-6 and TNF (each p = 0.001) was higher in samples from men than in those from women. Inhibition of lipopolysaccharide stimulated IL-6 and TNF release by either glucocorticoid was less pronounced in samples from men than in those from women (IL-6: dexamethasone p = 0.033, hydrocortisone p = 0.029; TNF: dexamethasone p < 0.001, hydrocortisone p = 0.089).

Conclusions: The finding suggests that proinflammatory activity of circulating monocytes is higher in men than in women independent of cardiovascular risk factors, thereby providing one explanation for the relatively greater coronary risk in men.

Abbreviations: ELISA, enzyme linked immunosorbent assay; HDL, high density lipoprotein; IC₅₀, concentration of dexamethasone or hydrocortisone that achieves a 50% inhibition of lipopolysaccharide stimulated cytokine release in the absence of any glucocorticoid; IL, interleukin; LDL, low density lipoprotein; MONICA, monitoring trends and determinants in cardiovascular disease; TNF, tumour necrosis factor

Keywords: glucocorticoid sensitivity; monocytes; cytokines; sex differences; cardiovascular disease

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