Project duration: 2000 – 2002
Funding: ETH Zurich, European Aeronautic Defense and Space Company (EADS)/Airbus Group SE

In this study, we examined the regulation of cytokyine release from monocytes in 330 industry workers. Among these, we identified individuals with increased cardiovascular risk. Besides classic risk factors such as exhaustion, gender and smoking, we also took more recent risk factors into account such as vital exhaustion and increased basal inflammatory status.
The reason for examining the regulation of proinflammatory cytokine release in individuals with increased cardiovascular risk is as follows: A certain sub-group of immune cells, the monocytes, play a crucial role in the development of arteriosclerosis, the process underlying cardiovascular disease. These cells release inflammatory messengers, i.e. inflammatory cytokines, which promote inflammation in arteriosclerotic lesions. Increased levels of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha or interleukin-6 are potentially associated with increased cardiovascular risk and heart attacks. This leads us to suppose that cytokine release from monocytes could contribute to increased cardiovascular risk.
The regulation of cytokine release from monocytes occurs as a consequence of both stimulation and inhibition. We used lipopolysaccaride (LPS) to stimulate cytokine release from monocytes, whereas glucocorticoids (i.e. stress hormones) were used to control stimulated cytocine release from monocytes.

Publications:
Wirtz, P.H., von Känel, R., Kunz-Ebrecht, S., Ehlert, U., Fischer, J.E (2004). Enhanced glucocorticoid sensitivity of cytokine release from monocytes stimulated with lipopolysaccharide in healthy male smokers. Brain Behav Immun 18(6):536-43. [Link]

Wirtz, P.H., von Känel, R., Frey, K., Rohleder, N., Fischer, J.E. (2004). Monocyte proinflammatory cytokine release is higher and glucocorticoid sensitivity is lower in middle-aged men than in women independent from cardiovascular risk factors. Heart 90(8):853-858. [Link]

Wirtz, P.H., von Känel, R., Frey, K., Ehlert, U., Fischer, J.E. (2004). Glucocorticoid sensitivity of circulating monocytes in essential hypertension. Am J Hypertens 17:489-494. [Link]

Wirtz, P.H., von Känel, R., Kunz-Ebrecht, S., Ehlert, U., Fischer, J.E. (2004). Reduced glucocorticoid sensitivity of monocyte interleukine-6 production in male industrial employees with high basal levels of tumor necrosis factor-alpha independent from other cardiovascular risk factors. Life Sci 75:1-10. [Link]

Wirtz, P.H., von Känel,  R., Schnorpfeil, P., Ehlert, U., Frey, K., Fischer, J.E. (2003). Reduced glucocorticoid sensitivity of monocyte interleukine-6 production in male industrial employees who are vitally exhausted. Psychosom Med 65(4):672-8. [Link]

Wirtz, P.H. (2002). Smoking, vital exhaustion and glucocorticoid sensitivity of pro-inflammatory cytokine release. Cross-sectional studies in apparently healthy male employees of the manufacturing industry. Göttingen: Cuvillier Verlag. [Link]