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Human immune cells mediate catecholamine secretion from adrenal chromaffin cells
H J Lujan1, H L Mathews, R L Gamelli
1University of Health Sciences/The Chicago Medical School, Mount Sinai Hospital Medical Center, IL, USA.
Insights
Human immune cells release factors that stimulate catecholamine secretion from adrenal cells, a process influenced by immune cell activation and steroid suppression. This immune-adrenal axis may play a role in critical illness.
Area of Science:
- Immunology
- Endocrinology
- Neuroscience
Background:
- The interaction between the immune and endocrine systems is crucial for maintaining homeostasis.
- Adrenomedullary chromaffin cells secrete catecholamines, vital hormones involved in the stress response.
- The role of immune cells in modulating catecholamine release is not fully understood.
Purpose of the Study:
- To investigate the capacity of human mononuclear cells to produce factors stimulating catecholamine secretion from adrenomedullary chromaffin cells.
- To identify conditions that enhance the production of these immune-derived factors.
- To compare immune cell-mediated catecholamine secretion with responses to known stimuli like interleukin (IL)-1, IL-2, and nicotinic agonists.
Main Methods:
- In vitro study utilizing human mononuclear cells and porcine chromaffin cells.
- Mononuclear cells were cultured, and their conditioned media were tested for catecholamine-releasing activity.
- Immune cell stimulation (phytohemagglutinin, mixed leukocyte reaction) and suppression (dexamethasone) were employed.
- Catecholamine secretion was measured via high-performance liquid chromatography with electrochemical detection.
Main Results:
- Human mononuclear cell conditioned media induced significant epinephrine and norepinephrine secretion from chromaffin cells (6.9% vs. 1.4% for control media, p < .05).
- Stimulation via mixed leukocyte reaction resulted in higher catecholamine release (16.6%) compared to single-donor media (6.9%, p < .001).
- Dexamethasone suppressed the release of bioactive products, while IL-1 and IL-2 did not significantly stimulate catecholamine secretion.
Conclusions:
- Human immune cells release non-neural factors that stimulate catecholamine release from adrenomedullary cells.
- Immune cell factor production is modulated by immunostimulation and steroid suppression.
- This immune-adrenal pathway may contribute to elevated circulating catecholamines during infection and critical illness.
Objectives:
To determine the ability of human mononuclear cells to produce factors that cause catecholamine secretion from adrenomedullary chromaffin cells; to determine conditions that stimulate mononuclear cells to produce such factors; and to compare these results with catecholamine secretion in response to the cytokines interleukin (IL)-1 and IL-2.
Design:
Randomized, controlled, prospective study using in vitro conditions.
Setting:
University research laboratory.
Subjects:
Human mononuclear cells and porcine chromaffin cells.
Interventions:
Circulating human mononuclear cells were isolated and cultured overnight in RPMI media. Cell-free media from these cultures (conditioned media) were then tested for the ability to cause epinephrine secretion from porcine chromaffin cells. Mononuclear cells were stimulated with phytohemagglutinin or by mixing cells from two different individuals while suppression was tested with dexamethasone. Catecholamine secretion in response to IL-1 and IL-2 (50 and 500 units/well, respectively), or nicotinic agonist dimethylphenylpiperazinium (10 microM, which mimics the action of acetylcholine), was tested for comparison.
Measurements And Main Results:
Isolated porcine chromaffin cells had stable catecholamine content at the time of secretion measurements, and catecholamine release from cells into the media was measured using electrochemical detection after high-performance liquid chromatography separation. Catecholamine secretion was expressed as a percentage of the total cellular content. Epinephrine secretion due to human conditioned media was 6.9 +/- 1.0% compared with 1.4 +/- 0.6% for control media (p < .05) and 14.6 +/- 3.3% for dimethylphenylpiperazinium (p < .05). Epinephrine secretion with conditioned media from mixed cells (mixed leukocyte reaction) was 16.6 +/- 1.2%, which was higher than the epinephrine secretion caused by media from a single donor (6.9% +/- 1.0, p < .001). Pretreatment with dexamethasone inhibited the formation of bioactive products from mixed mononuclear cell preparations. Cytokines IL-1 and IL-2 did not stimulate chromaffin cell epinephrine secretion above background release with control media incubation. In all cases, norepinephrine secretion was similar to that of epinephrine, and results are included in all figures.
Conclusions:
Factors released from human immune cells can mediate epinephrine and norepinephrine release from adrenomedullary cells through a nonneural mechanism. Such immune cell factor release can be modulated by immunostimulation and steroid suppression. Release of such factors in vivo may contribute to increased circulating epinephrine in response to infectious challenge and may be an important factor in the critically ill patient.