TEMPERATURE-INDUCED DOWN-REGULATION OF THE GLUCOCORTICOID RECEPTOR INPERIPHERAL-BLOOD MONONUCLEAR LEUKOCYTE IN PATIENTS WITH SEPSIS OR SEPTIC SHOCK

OBJECTIVE Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness. We have studied the adaptive mechanisms which occur at the level of the glucocorticoid receptor in glucocorticoid target tissues in patients with sepsis or septic shock . DESIGN The effects of hypercortisolaemia, hyperthermia and cellular composition on number of glucocorticoid receptors per cell and their a ffinity were evaluated, both in vitro and in vivo, in peripheral blood mononuclear leucocytes of control subjects and in patients with sepsi s or septic shock. SUBJECTS Fifteen patients (age 25-79) with sepsis o r septic shock who were admitted to an intensive care unit were studie d. The control group consisted of 24 healthy laboratory employees. MEA SUREMENTS The binding capacity and affinity of the glucocorticoid rece ptors were measured and compared to clinical data and the plasma corti sol concentrations. RESULTS Hypercortisolaemia, in vitro, resulted in a decreased affinity and a decreased binding capacity of the glucocort icoid receptor. In vitro, hyperthermia as well as variations in the ce llular composition did not influence the glucocorticoid receptor. In v ivo, there was no change in the number of receptors per cell in patien ts with sepsis or septic hock as compared to healthy controls. However , a decreased affinity of the glucocorticoid receptor was observed. Th ere was a weak but significant negative correlation between body tempe rature and the number of glucocorticoid receptors in the patient group . There was no relation between circulating cortisol concentrations an d glucocorticoid receptor affinity and number. CONCLUSIONS There is no obvious regulation of the number of glucocorticoid receptors by plasm a cortisol concentrations in vivo. The decreased affinity of the gluco corticoid receptor together with the negative correlation between hype rthermia and the number of glucocorticoid receptors in patients with s epsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adapt ation in glucocorticoid receptor number and affinity.