Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels

The influence of acute mental stress on cardiovascular responses and concentrations of inflammatory cytokines up to 2 h later was assessed in 12 subjects exposed to stress and in eight control subjects. Beat-by-beat recordings of finger blood pressure and heart rate were made at rest and during two behavioural tasks (colour-word interference and mirror tracing). Blood was drawn after adaptation and at 45 min and 2 h after the tasks, and assayed for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-I Ra), C-reactive protein (CRP) and haematocrit. Saliva was sampled periodically and assayed for free cortisol. The tasks were rated as stressful by the participants. The stress group showed significant increases in systolic and diastolic blood pressure (mean rises of 16.4 +/- 12.3 and 12.6 +/- 6.9 mmHg respectively) and heart rate (5.39 +/- 5.3 beats/min); these values returned to baseline during the recovery period. The IL-6 concentration was increased by 56% at 2 h after the tasks (P < 0.05), while IL-1Ra was increased by 12.3% (P < 0.01). No changes in cardiovascular variables or cytokine concentrations were observed in the control subjects, and haematocrit did not change. The magnitude of blood pressure responses during tasks was correlated positively with the IL-6 concentration after 45 min (r = 0.70, P < 0.05), and with the IL-1Ra concentration after 2 h (r = 0.63, P < 0.05). Increases in TNF-alpha after 2 h were correlated with heart rate responses to tasks (r = 0.66, P < 0.05). Associations between IL-6 and IL-I Ra concentrations were also recorded. This study indicates that inflammatory cytokines respond to acute mental stress in humans with delayed increases, and suggest that individual differences in cytokine responses are associated with sympathetic reactivity.