Psychological stress activates interleukin-1β gene expression in human mononuclear cells

The pathophysiological mechanisms underlying the association between psychological stress and cardiovascular disease are unclear. Interleukin-1β (IL-1β) and interleukin-6 (IL-6) are inflammatory cytokines playing a pivotal role in atherosclerosis. IL-1β activates IL-6, and both cytokines are produced by peripheral blood mononuclear cells. One mechanism through which stress could promote atherosclerosis is by regulating mononuclear cell cytokine gene expression. We studied cardiovascular and cytokine responses in 32 healthy men participating in two 5-min mental tasks and in 10 controls. Blood pressure and heart rate, assessed using a Portapres-2, increased significantly following tasks in all participants. Plasma IL-6 levels, determined by ELISA, also increased following tasks, with maximum levels detected 2 h post-stress. Quantitative RT-PCR analysis showed that mononuclear cell IL-1β gene expression rose significantly at 30 min post-stress and remained elevated at 75 and 120 min. Increases in IL-1β gene expression correlated positively with plasma IL-6 responses, cardiovascular responses, subjective stress ratings, and anxiety symptoms. No changes were detected in controls. Stress-induced activation of mononuclear IL-1β is a novel mechanism potentially linking stress and heart disease. This mechanism could also play a role in other inflammatory diseases exacerbated by stress.