Effect of immunomodulators pyrimethamine and cimetidine on immunosuppression induced by sulfur mustard in mice

A corticotropin-releasing hormone (CRH) stimulation test with four cumulative doses of human CRH (0.01, 0.06, 0.2 and 1 microgram/kg body weight) and infusion of a low dose of Arg8]-vasopressin (0.004 U/kg body weight/30 min) was performed in five depressed patients and six healthy subjects. Plasma samples for the measurement of cortisol, ACTH and beta-endorphin were taken at regular intervals and considered as measures of pituitary-adrenal function. A dose-response relationship between CRH and the hormones measured was found in patients and controls. Depressed patients already responded to the lowest dose of CRH with respect to cortisol release, whereas ACTH and beta-endorphin responded to the second and third doses, respectively. In control subjects the cortisol and ACTH response started after the third dose of CRH, whereas beta-endorphin responded significantly to the highest dose only. When both groups were compared, differences in response were found to the higher doses of CRH with respect to cortisol, ACTH and, less markedly, beta-endorphin and to the lowest dose of CRH with respect to cortisol. Although numbers are small, the data show 'blunting' of the ACTH response to the higher doses of CRH in patients with an enhanced cortisol response of the adrenals to lower and higher doses of CRH. There was no significant difference in response when CRH was used with vasopressin as compared to treatment with CRH alone. Thus, in this design vasopressin did not contribute significantly to CRH activity. The data suggest that pituitary cell sensitivity might be changed in depression as part of HPA dysfunction.