Stress-induced modulation of NF-κB activation, inflammation-associated gene expression, and cytokine levels in blood of healthy men

Abstract

Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines, but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms. We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level. Forty-five healthy men were randomly assigned to either a stress or control group. While the stress group underwent an acute psychosocial stress task, the second group participated in a non-stress control condition. We repeatedly measured before and up to 120min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, whole-blood mRNA levels of NF-κB, its inhibitor IκBα, and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6, and the anti-inflammatory cytokine IL-10. We also repeatedly measured plasma levels of IL-1ß, IL-6, and IL-10. Compared to non-stress, acute stress induced significant and rapid increases in NF-κB-BA and delayed increases in plasma IL-6 and mRNA of IL-1ß, IL-6, and IκBα (p's<.045). In the stress group, significant increases over time were also observed for NF-κB mRNA and plasma IL-1ß and IL-10 (p's<.055). NF-κB-BA correlated significantly with mRNA of IL-1β (r=.52, p=.002), NF-κB (r=.48, p=.004), and IκBα (r=.42, p=.013), and marginally with IL-6 mRNA (r=.31, p=.11). Plasma cytokines did not relate to NF-κB-BA or mRNA levels of the respective cytokines. Our data suggest that stress induces increases in NF-κB-BA that relate to subsequent mRNA expression of pro-inflammatory, but not anti-inflammatory cytokines, and of regulatory-cytoplasmic-proteins. The stress-induced increases in plasma cytokines do not seem to derive from de novo synthesis in circulating blood cells.

Acute and chronic psychological stress as risk factors for cardiovascular disease: Insights gained from epidemiological, clinical and experimental studies

“…Heart; blood Stress duration dependent " plasma CORT; ; heart histamine level; " serum histamine level; " mast cell degranulation Huang et al " plaque size; " hematopoietic system activity; " plaque protease levels; " intimal neutrophils, monocytes and macrophages; " necrotic core area; ; fibrous cap thickness; " plaque monocyte inflammatory gene expression No significant difference in bodyweight; total cholesterol Dutta et al (2012) Similar to the response to chronic stress, acute stress exposure has been demonstrated to result in a quick rise in plasma interleukins and inflammatory markers (Table 1) (Yamauchi et al, 2013;Wilbert-Lampen et al, 2010;Schultze-Florey et al, 2012;Cohen et al, 2015;Suarez, 2004;Coccaro et al, 2014;Slavish et al, 2015), such as IL-6, IL-1b and sICAM (Heinz et al, 2003;Kuebler et al, 2015), which have all been demonstrated to be proatherogenic. Furthermore, the rise in plasma IL-6 was seen to associate with fibrin formation and pro-coagulant markers (von Känel et al, 2005), which may lead to an enhanced risk of thrombosis upon plaque rupture.…”

Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men

“…Evidence shows that the binding activity of the nuclear factor-kappaB (NF-kB), a key mediator of inducible transcription in the immune system and inflammatory genes, is enhanced by exposure to acute stress in humans. This is likely mediated through adrenergic receptor stimulation [4,6,7] and appears to be inversely related to glucocorticoid responses [7,8].…”

Are Inflammatory Cytokines Associated with Pain during Acute Myocardial Infarction?

“…Both acute and chronic psychosocial stress have been associated with the release of proinflammatory cytokines, e.g., TNF-α and IL-6 [12][13][14][15] , and, as mentioned above, pain and acute psychological distress are correlated during AMI.…”