In vitro dexamethasone suppression of cytokine production assay and plasma total and free cortisol responses to ACTH in healthy volunteers

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Glucocorticoid sensitivity varies between individuals, influencing stress and inflammatory responses, however its relationship with the synthetic ACTH [1-24] stimulation test, is not well evaluated. To evaluate glucocorticoid sensitivity and plasma total cortisol (TC) and plasma free cortisol (PFC) responses to stimulation with 250 μg of synthetic ACTH [1-24]) in healthy adults. Prospective, single-centre observational study. Forty-eight healthy adults (24 females, 24 males) underwent basal and stimulated TC and PFC level measurements using liquid chromatography-tandem mass spectrometry. Peak cortisol values were defined as the highest TC or PFC at either 30- or 60-min. Glucocorticoid sensitivity was measured using the dexamethasone suppression of cytokine production (DSCP) assay, based on interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) production from lipopolysaccharide-stimulated (LPS) monocytes. A whole blood sample was incubated with buffer, LPS, or LPS with dexamethasone (Dex). TNF-α and IL-6 concentrations were measured in the supernatants (ng/L). The ratio of cytokine levels between LPS + Dex and LPS indicated glucocorticoid sensitivity. Data from 45 participants were analysed. Peak TC levels ranged from 391 to 1570 nmol/L (median: 618 nmol/L, IQR: 555-729), while PFC levels ranged from 27 to 133 nmol/L (median: 62 nmol/L, IQR: 53-73). No significant associations were found between baseline or peak TC and PFC levels and glucocorticoid sensitivity ratios. Synthetic ACTH (1-24) test results did not predict glucocorticoid sensitivity. Males exhibited higher BMI (median: 26 vs. 22; p = 0.031), however no significant differences were observed in age, baseline PFC and TC levels between sexes. In this exploratory study, ACTH [1-24]-stimulated cortisol responses did not correlate with glucocorticoid sensitivity measured by the DSCP assay. Findings should be interpreted as preliminary and hypothesis-generating given current assay limitations.

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