SFEBES2017 Poster Presentations Adrenal and Steroids (33 abstracts)
The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to establish homeostasis during the stress of critical illness and surgery. However, such critical states also trigger a systemic inflammatory activation that usually precedes the release of adrenocorticotrophic hormone (ACTH) and cortisol. Systemically or locally induced inflammation of the adrenal gland had been described during critical illness. This facilitates an immune-adrenal cross-talk that could modulate cortisol release in this condition.
We demonstrate that immortalised murine adrenocortical ATC7 cells do not show a significant activation of pro-inflammatory cytokines in response to inflammatory stress (lipopolysaccharide, LPS). There was no significant increase in the expression of both interleukin-6 mRNA and protein, and neither co-treatment with ACTH nor interferon gamma had any effect on interleukin-6 mRNA expression. Furthermore, there was no significant effect in the regulation of the key steroidogenic genes in response to these treatments. This led us to hypothesise that immune-effector cells might play a central role in the modulation of both the inflammatory and steroidogenic pathways within the adrenal cells. We therefore developed a novel trans-well co-incubation model of THP1 (human monocytic cell)-derived macrophages and ATC7 cells. We demonstrate a significant surge of IL-6 mRNA in ATC7 cells as a result of co-incubation with the THP1 cells, and this effect was potentiated by treatment with LPS. Furthermore, we also found significant changes in key steroidogenic enzymes (including StAR and DAX-1). Moreover, 24-hour co-incubation with glucocorticoid prevented, in a dose related manner, the IL6 mRNA increase induced by LPS stimulation.
Our co-incubation model suggests that the expression of inflammatory cytokines in adrenal cells is immune-dependent. Furthermore, glucocorticoids can regulate this immune-adrenal interaction with implications to clinical practice. More studies, aimed at the changes within the THP1 cells are needed to elucidate this interaction.
06 Nov 2017 - 08 Nov 2017