The effects of acute psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis

Inflammatory reactivity to acute laboratory stress is thought to reflect individual differences in responsivity to environmental stressors and may confer future health risk. To characterize this response, we conducted a meta-analysis of 34 studies that measured circulating inflammatory markers and 15 studies that measured stimulated production of inflammatory markers before and after exposure to laboratory challenge. Results showed significant stress-related increases in circulating interleukin (IL)-1β (d=0.66, p<0.001), IL-6 (d=0.35, p<0.001), IL-10 (d=0.69, p<0.001), and tumor necrosis factor(TNF)-α (d=0.28, p<0.001), but not IL-1ra, IL-2, interferon-γ, or C-reactive protein. There were sufficient data to assess the time course of IL-6, IL-1β, and TNF-α reactivity. IL-6 increased from baseline to measures taken 40-50, 60-75, 90, and 120min following stress, with the largest effect at 90min post-stress (d=0.70, p<0.001). IL-1β increased from baseline to 20-30, 40-50, and 60-70min following stress, with the largest effect between 40 and 50min post-stress (d=0.73, p=0.02). For TNF-α, there was a significant increase from baseline to 31-50min post stress (d=0.44, p=0.01), but not at later times. There was no difference in magnitude of IL-6 reactivity as a function of type of stress (social-evaluative versus other). For stimulated inflammatory markers, results showed stress-related increases in IL-1β when measured 20-120min post-stress (d=1.09, p<0.001), and in IL-4 and interferon-γ when measured 0-10min post stressor (d=-0.42, p<0.001 and d=0.47, p<0.001). These results extend findings from a prior meta-analysis (Steptoe et al., 2007) to show reliable increases in circulating IL-6, IL-1β, IL-10 and TNF-α and stimulated IL-1β, IL-4 and interferon-γ in response to acute stress. It is possible that these responses contribute to associations between exposure to life challenges and vulnerability to inflammatory disease.