Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines

Bailey

Psychoneuroendocrinology

et al. 2008

SummaryFrequent or chronic stress as a result of repeated or persistent exposure to social challenges has been shown to affect the glucocorticoid (GC) responsiveness of immune cells in mice. Lipopolysaccharide-stimulated splenocytes of mice that were repeatedly subjected to social disruption were less sensitive to the anti-inflammatory actions of GC as evident from an increased production of pro-inflammatory cytokines and enhanced cell survival. The development of functional GC resistance was accompanied by the accumulation of GC-insensitive CD11b + cells in the spleen. These cells were shown to exhibit impaired nuclear translocation of the GC receptor and lack of GCinduced suppression of NF-κB. Similar impairments in GC receptor function have been reported after in vitro treatment of various cell lines with interleukin (IL)-1. The aim of this study was to elucidate whether IL-1 is a critical factor for the development of GC resistance in socially stressed mice. In the first experiment, we investigated if repeated social stress alters plasma levels and tissue gene expression of IL-1α and IL-1β. It revealed that recurrent stressor exposure significantly increased splenic and hepatic mRNA expression and the plasma protein level of IL-1β, and hepatic mRNA expression of IL-1α. In the second experiment, IL-1 receptor type 1 (IL1R1)-deficient mice were subjected to the stressor and both the tissue distribution of CD11b + cells and the GC sensitivity of the splenocytes were compared to wildtype mice. Mice lacking the IL1R1 exhibited adrenal hypertrophy, thymic involution, and elevated serum corticosterone levels in response to the stressor but did not show splenic accumulation of CD11b + cells and failed to develop GC resistance. These findings suggest that IL-1 plays a critical role in the development of the social stress-associated GC resistance in the murine spleen.

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 96%

Interleukin-1 receptor type 1-deficient mice fail to develop social stress-associated glucocorticoid resistance in the spleen

Bailey

Psychoneuroendocrinology

et al. 2008

“…Indeed, we have preliminary data suggesting that the observed changes in BDNF mRNA produced by the combination of IS plus fluoxetine are followed by similar changes in BDNF protein (Campisi et al, 2005).…”

Section: The Role Of Bdnf In the Protective Effect Of Wheel Running Amentioning

confidence: 73%

“…Rats were killed by decapitation and the hippocampus and PFC were hand dissected on a frosted glass plate over ice as previously described (Johnson et al, 2004, Johnson et al, 2005. Hippocampus and PFC were placed in microfuge tubes and quickly frozen in liquid nitrogen and stored at −80°C until quantification of BDNF protein.…”

Section: Assessment Of Bdnf Proteinmentioning

confidence: 99%

Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus

et al. 2007

Self Cite

Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against stress-induced reductions of hippocampal BDNF protein.The observed prevention of stress-induced deceases in BDNF, however, occurred in a time course inconsistent with the prevention of learned helplessness by wheel running, which is evident following 6 weeks, but not 3 weeks, of wheel running. BDNF suppression in physically active rats was produced by administering a single injection of the selective serotonin reuptake inhibitor fluoxetine (10 mg/ kg) just prior to stress. Despite reduced levels of hippocampal BDNF mRNA following stress, physically active rats given the combination of fluoxetine and stress remained resistant against learned helplessness. Sedentary rats given both fluoxetine and stress still demonstrated typical learned helplessness behaviors. Fluoxetine by itself reduced BDNF mRNA in sedentary rats only, but did not affect freezing or escape learning 24 hours later. Finally, bilateral injections of BDNF (1 μg) into the dentate gyrus prior to stress prevented stress-induced reductions of hippocampal BDNF but did not prevent learned helplessness in sedentary rats.These data indicate that learned helplessness behaviors are independent of the presence or absence of hippocampal BDNF because blocking inescapable stress-induced BDNF suppression does not always prevent learned helplessness, and learned helplessness does not always occur in the presence of reduced BDNF. Results also suggest that the prevention of stress-induced hippocampal BDNF suppression is not necessary for the protective effect of wheel running against learned helplessness.

Brain, Behavior, and Immunity

“…For example, stress-induced increases in NFκB signaling were modeled in human monocyte THP-1 cells after stimulation with norepinephrine, suggesting that SNS activation may be responsible for stress-induced cytokine increases (Bierhaus et al 2003). Injection of alpha and beta adrenoceptor antagonists block the stress-mediated increase in IL-1β levels, and adrenoceptor agonists are sufficient to substitute for stress (Johnson et al 2005). Because the actions of catecholamines are exerted on a shorter timescale than those of GCs, these results fit with the picture of acute and early stages of stress as pro-inflammatory.…”

Section: The Pro-inflammatory Effects Of Stress Outside the Nervous Smentioning

confidence: 99%

An inflammatory review of glucocorticoid actions in the CNS

Sorrells¹,

Sapolsky²

2007

397

283

In recent years the classic view that glucocorticoids, the adrenal steroids secreted during stress, are universally anti-inflammatory has been challenged at a variety of levels. It was first observed that under some circumstances, acute GC exposure could have pro-inflammatory effects on the peripheral immune response. More recently, chronic exposure to GCs has been found to have pro-inflammatory effects on the specialized immune response to injury in the central nervous system. Here we review the evidence that in some cases, glucocorticoids can increase pro-inflammatory cell migration, cytokine production, and even transcription factor activity in the brain. We consider how these unexpected effects of glucocorticoids can co-exist with their well-established anti-inflammatory properties, as well as the considerable clinical implications of these findings.