ENDOTOXIN-RELEASING AND CORTICOTROPIN-RELEASING HORMONE-INDUCED RELEASE OF ACTH AND CORTISOL - A COMPARATIVE-STUDY IN MEN

The present study compares the effects of endotoxin, a key factor in g ram-negative bacterial infection, and of corticotropin-releasing hormo ne (CRH) on ACTH and cortisol secretion in healthy male volunteers in a placebo-controlled design. Endotoxin (isolated from Salmonella abort us equi,- 0.4 ng/kg body weight) induced a significantly delayed and p rolonged increase of ACTH and cortisol secretion as compared to CRH (1 00 mug), supporting the hypothesis that different intermediate mechani sms are involved (baseline/peak: ACTH(Endotoxin) vs. ACTH(CRH): 140 +/ - 40 min vs. 44 +/- 17 min (p < 0.001); Cortisol(Endotoxin) vs. Cortis ol(CRH): 113 +/- 51 min vs. 66 +/- 31 min (p < 0.05); peak/baseline: A CTH(Endotoxin) vs. ACTH(CRH): 244 +/- 79 min vs. 200 +/- 25 min (p < 0 .05); Cortisol(Endotoxin) vs. Cortisol(CRH): 278 +/- 76 min vs. 182 +/ - 16 min (p < 0.001)). Activation of the hypothalamo-pituitary-adrenoc ortical (HPA) system by endotoxin in men is associated with increased interleukin-6 (peak value: 124 +/- 109 pg/ml) and tumor necrosis facto r-alpha (peak value: 69 +/- 53 pg/ml) plasma levels which, probably to gether with locally produced interleukin-1, stimulate the HPA system b oth at the hypothalamic and (to a lesser degree) at the pituitary site . Provided that strictly controlled laboratory conditions are applied, the endotoxin challenge test presented here may serve as an appropria te and safe tool to explore an individual's capacity for neuroendocrin e adaptation to a bacterial stressor, thus providing information compl ementary to the CRH test.