HUMAN IMMUNE CELLS MEDIATE CATECHOLAMINE SECRETION FROM ADRENAL CHROMAFFIN CELLS

Objectives: To determine the ability of human mononuclear cells to pro duce factors that cause catecholamine secretion from adrenomedullary c hromaffin cells; to determine conditions that stimulate mononuclear ce lls to produce such factors; and to compare these results with catecho lamine secretion in response to the cytokines interleukin (IL)-1 and I L-2. Design: Randomized, controlled, prospective study using in vitro conditions. Setting: University research laboratory. Subjects: Human m ononuclear cells and porcine chromaffin cells. Interventions: Circulat ing human mononuclear cells were isolated and cultured overnight in RP MI media. Cell-free media from these cultures (conditioned media) were then tested for the ability to cause epinephrine secretion from porci ne chromaffin cells. Mononuclear cells were stimulated with phytohemag glutinin or by mixing cells from two different individuals while suppr ession was tested with dexamethasone. Catecholamine secretion in respo nse to IL-1 and IL-2 (50 and 500 units/well, respectively), or nicotin ic agonist dimethylphenylpiperazinium (10 mu M, which mimics the actio n of acetylcholine), was tested for comparison. Measurements and Main Results: isolated porcine chromaffin cells had stable catecholamine co ntent at the time of secretion measurements, and catecholamine release from cells into the media was measured using electrochemical detectio n after high-performance liquid chromatography separation, Catecholami ne secretion was expressed as a percentage of the total cellular conte nt, 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) wa s 16.6 +/- 1.2%, which was higher than the epinephrine secretion cause d 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 s timulate chromaffin cell epinephrine secretion above background releas e with control media incubation, In all cases, norepinephrine secretio n was similar to that of epinephrine, and results are included in all figures. Conclusions: Factors released from human immune cells can med iate epinephrine and norepinephrine release from adrenomedullary cells through a nonneural mechanism. Suck immune cell factor release can be modulated by immunostimulation and steroid suppression. Release of su ch 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.