Glucocorticoids enhance the in vivo migratory response of human monocytes

Abstract

Glucocorticoids (GCs) are best known for their potent anti-inflammatory effects. However, an emerging model for glucocorticoid (GC) regulation of in vivo inflammation also includes a delayed, preparatory effect that manifests as enhanced inflammation following exposure to an inflammatory stimulus. When GCs are transiently elevated in vivo following exposure to a stressful event, this model proposes that a subsequent period of increased inflammatory responsiveness is adaptive because it enhances resistance to a subsequent stressor. In the present study, we examined the migratory response of human monocytes/macrophages following transient in vivo exposure to stress-associated concentrations of cortisol. Participants were administered cortisol for 6 hours to elevate in vivo cortisol levels to approximate those observed during major systemic stress. Monocytes in peripheral blood and macrophages in sterile inflammatory tissue (skin blisters) were studied before and after exposure to cortisol or placebo. We found that exposure to cortisol induced transient upregulation of monocyte mRNA for CCR2, the receptor for monocyte chemotactic protein-1 (MCP-1/CCL2) as well as for the chemokine receptor CX3CR1. At the same time, mRNA for the transcription factor IκBα was decreased. Monocyte surface expression of CCR2 but not CX3CR1 increased in the first 24 hours after cortisol exposure. Transient exposure to cortisol also led to an increased number of macrophages and neutrophils in fluid derived from a sterile inflammatory site in vivo. These findings suggest that the delayed, pro-inflammatory effects of cortisol on the human inflammatory responses may include enhanced localization of effector cells at sites of in vivo inflammation.

Randomized field trial on the effects of body weight and short transport on stress and immune variables in 2‐ to 4‐week‐old dairy calves

“…To explain the observed differences between transported and control animals and low and normal body weight calves, the most likely mechanism is the effect of serum cortisol concentration. Depending on the concentration, cortisol can have suppressive, stimulatory, and also preparatory effects on the immune system. Preparatory effects can be observed when a transient (hours) in vivo exposure to stress‐induced GC concentrations is followed by a return to normal, basal concentrations and are caused by transcriptional and phenotypic changes in immune effector cells that prime them for enhanced responses to a subsequent immune stimulus .…”

“…Depending on the concentration, cortisol can have suppressive, stimulatory, and also preparatory effects on the immune system. Preparatory effects can be observed when a transient (hours) in vivo exposure to stress‐induced GC concentrations is followed by a return to normal, basal concentrations and are caused by transcriptional and phenotypic changes in immune effector cells that prime them for enhanced responses to a subsequent immune stimulus . These effects typically manifest several hours after transient exposure to stress‐increased GCs and might last for up to a week .…”

“…In our study, preparatory effects are suspected from 5 hours after transport on, when serum cortisol concentration is back to basal concentrations. With LPS‐ and BG‐stimulation, we mimicked an inflammatory stimulus within this period, resulting in a pro‐inflammatory reaction (IL‐17A and TNF‐α). Possibly, low body weight calves respond earlier and more vigorously than normal body weight calves.…”

Cold water immersion: kill or cure?

“…This has not been investigated in the context of CWI, but Yeager et al . () found that monocytes and neutrophils did indeed migrate into sterile blister fluid in response to a dose of cortisol corresponding to that released during acute stress. The 29% increase in resting monocyte levels over 6 weeks of CWI reported by Janský et al .…”

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

“…49,50 This suggests that a Dex-dependent decrease in serum MCP-1 may be compensated for by an increase in CCR2. Consistent with this, flow cytometric analysis of circulating monocytes revealed that Dex-naïve GBM patients have fewer CCR2+ cells, but Dex treatment restored CCR2 frequencies to those seen in healthy donors (Figure 4G).…”