Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans

Abstract

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as ‘sickness behaviour’. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants’ serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Differential Effects of Inflammatory and Psychosocial Stress on Mood, Hypothalamic-Pituitary-Adrenal Axis, and Inflammation in Remitted Depression

“…In the present study, no effect of inflammatory stress on mood was found in controls; however, other studies [17,19,20,40,41,42,43], although not all [44], observed negative effects of inflammation in healthy controls. Interestingly, personality traits such as optimism protect against inflammation-induced mood decreases [45].…”

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

“…In particular, stress is an important confounding factor because it induces an increase in pro-inflammatory cytokine levels in the blood. 129,130 This result has also been demonstrated for depression, which has been associated with disturbances in pro-inflammatory cytokine levels and circulating immune cells. 121,122 In addition, disturbances in trypto-phan metabolism have been described in affective disorders [131][132][133] and are thus very likely to impact 5HT levels.…”

Effects of Acute Stress-Induced Immunomodulation on Th1/Th2 Cytokine and Catecholamine Receptor Expression in Human Peripheral Blood Cells

“…Recent reports indicate that acute psychosocial stressors were found to upregulate protective cytokine and protective behavioral responses to immune stimuli in rodents [22,23] . However, psychological and immune stressors can also act synergistically to promote inflammation and sickness behavior in humans which ultimately can be, if self-limited, protective to the host [24] . Cytokines mediate and control immune and inflammatory responses.…”