Abstract

Psychosocial stress might increase the risk of atherothrombotic events by setting off an elevation in circulating levels of the proinflammatory cytokine interleukin (IL)-6. We investigated the effect of aspirin and propranolol on the responsiveness of plasma IL-6 levels to acute psychosocial stress. For 5 days, 64 healthy subjects were randomized, double-blind, to daily oral aspirin 100 mg plus long-acting propranolol 80 mg, aspirin 100 mg plus placebo, long-acting propranolol 80 mg plus placebo, or placebo plus placebo. Thereafter, all subjects underwent the 13-min Trier Social Stress Test, which combines a preparation phase, a job interview, and a mental arithmetic task. Plasma IL-6 levels were measured in blood samples collected immediately pre- and post-stress, and 45 min and 105 min thereafter. The change in IL-6 from pre-stress to 105 min post-stress differed between subjects with aspirin medication and those without (p = 0.033;  = 0.059). IL-6 levels increased less from pre-stress to 105 min post-stress (p < 0.027) and were lower (p = 0.010) at 105 min post-stress in subjects with aspirin than in subjects without aspirin. The significance of these results was maintained when controlling for gender, age, waist-to-hip ratio, mean arterial blood pressure, and smoking status. Medication with propranolol was not significantly associated with the stress-induced change in IL-6 levels. Also, aspirin and propranolol did not significantly interact in determining the IL-6 stress response. Aspirin but not propranolol attenuated the stress-induced increase in plasma IL-6 levels. This suggests one mechanism by which aspirin treatment might reduce the risk of atherothrombotic events triggered by acute mental stress.

Keywords: Cardiovascular disease; Cytokines; Drugs; Psychological stress

Article Outline

1. Introduction

2. Methods

2.1. Study participants and recruitment

2.2. Medical data

2.3. Study medication

2.4. Stress protocol

2.5. Biochemical measures

2.6. Statistical analyses

3. Results

3.1. Subject characteristics

3.2. Bivariate associations with resting levels of IL-6

3.3. Effect of medication on IL-6, blood pressure, and cortisol at rest

3.4. Blood pressure and cortisol reactivity

3.5. Interleukin-6 stress reactivity

3.5.1. Repeated measures analyses of variance

3.5.2. Repeated measures analyses of covariance

3.5.3. Complementary analyses

4. Discussion

Acknowledgements

References