Introduction: Proinflammatory cytokines, for example interleukin-6, have been found to stimulate the HPA axis at all levels. In animal models glucocorticoids have been shown to suppress cytokines. There may therefore be a balanced interaction during stress when both are raised. For this reason, we investigated patients undergoing routine coronary artery bypass grafting on day 3 post-operatively (CABG) to examine the mechanisms for failure of suppression of the HPA axis in response to 1 milligram of dexamethasone (DXT). St. Thomas' Hospital ethics committee approved the study. Method: Hospital staff (19) and CABG subjects (12) were studied. Basal ACTH, cortisol and IL-6 levels were measured. A similar cohort of controls (13) and patients (10) were examined following 1 milligram of DXT. An extraction RIA for DXT and standard chemiluminescent assays were employed. Results: ACTH, cortisol and IL-6 were suppressed in controls following DXT, from 31 plus/minus 4 (SEM) to 8 plus/minus 1 nanograms per litre (p<0.001) from 380 plus/minus 25 to 35 plus/minus 6 nanomoles per litre (p<0.001) and from 3 plus/minus 0.4 to 0.03 plus/minus 0.02 picograms per millilitre (p<0.001) respectively. Basal compared with post-DXT CABG ACTH, cortisol and IL-6 levels were 27 plus/minus 4 vs 12 plus/minus 3 nanograms per litre (p<0.01), 467 plus/minus 33 vs 275 plus/minus 79 nanomoles per litre (p=0.02) and 39 plus/minus 7 vs 8 plus/minus 3 picograms per millilitre (p<0.001) respectively. Conclusion: DXT suppressed ACTH levels as effectively in CABG patients as in controls. In contrast, cortisol and IL-6 levels, although significantly suppressed remained grossly elevated compared with controls. Incomplete cortisol suppression in the CABG patients may be due to direct adrenal-cortical stimulation by IL-6. Measurement of post-DXT IL-6 may help to identify patients with false positive DXT suppression tests when screening for Cushing's disease.
03 - 04 Dec 2001
Society for Endocrinology