Cortisol-dependent stress effects on cell distribution in healthy individuals and individuals suffering from chronic adrenal insufficiency

Abstract

Chronic adrenal insufficiency (CAI) is characterized by a lack of glucocorticoid and mineralocorticoid production due to destroyed adrenal cortex cells. However, elevated cortisol secretion is thought to be a central part in a well-orchestrated immune response to stress. This raises the question to what extent lack of cortisol in CAI affects stress-related changes in immune processes. To address this question, 28 CAI patients (20 females) and 18 healthy individuals (11 females) (age: 44.3 ± 8.4 years) were exposed to a psychosocial stress test (Trier Social Stress Test: TSST). Half the patients received a 0.03 mg/kg body weight injection of hydrocortisone (HC) post-TSST to mimic a healthy cortisol stress response. Catecholamines and immune cell composition were assessed in peripheral blood and free cortisol measured in saliva collected before and repeatedly after TSST. CAI patients showed norepinephrine (NE) stress responses similar to healthy participants, however, epinephrine (E) as well as cortisol levels were significantly lower. HC treatment post-TSST resulted in cortisol increases comparable to those observed in healthy participants (interaction effects--NE: F=1.05, p=.41; E: F=2.56, p=.045; cortisol: F=13.28, p<.001). Healthy individuals showed the expected pattern of stress-related early lymphocyte increase with subsequent decrease below baseline. The opposite pattern was observed in granulocytes. While exhibiting a similar initial increase, lymphocytes kept increasing over the following 2h in untreated patients. HC treatment buffered this effect (interaction effects--lymphocyte%: F=7.31, p<.001; granulocyte%: F=7.71, p<.001). Using CAI in humans as a model confirms cortisol's central involvement in post-stress lymphocyte migration from blood into immune-relevant body compartments. As such, future studies should investigate whether psychosocial stress exposure may put CAI patients at an increased health risk due to attenuated immune responses to pathogens.

Keywords: Catecholamines; Cell trafficking; Chronic adrenal insufficiency; Cortisol; Psychosocial stress.

Fig. 1

Study protocol diagram indicating blood and saliva collection times relative to TSST exposure. ^*HC or NaCl injection.

Fig. 2

Comparisons of cortisol and catecholamine stress responses across the three study groups. Note: HP-NaCl = placebo-treated healthy participants; CAI-HC = CAI patients treated with hydrocortisone; CAI-NaCl = placebo-treated CAI patients.

Fig. 3

Changes in cell counts in response to stress for each of the study groups. Note: HP-NaCl = placebo-treated healthy participants; CAI-HC = CAI patients treated with hydrocortisone; CAI-NaCl = placebo-treated CAI patients.

Fig. 4

Group comparisons of stress-related changes in lymphocyte percentages (left) and granulocyte percentages (right). Note: HP-NaCl = placebo-treated healthy participants; CAI-HC = CAI patients treated with hydrocortisone; CAI-NaCl = placebo-treated CAI patients.