Thus, our description of HPA axis rather corresponds to the post-acute phase of sepsis in the experimental model, while that in septic patients to the ultimate phase. This difference may explain the finding that expression of CRH was greater in rats than in humans. PD325901 Interestingly, a previous experimental study showed that parvocellular CRH expression peaked 24 hours after onset of CLP, suggesting that animals died in the post-acute phase of septic shock. To our knowledge there is no study that correlates neuropathological findings in HPA axis with the severity of the septic shock. It was not possible to determine whether the absence of increase in CRH depends on septic shock duration, intensity or both since all patients died from severe septic shock. The finding that CRH expression did not vary among patients according to the duration of septic shock supports that sepsis intensity was a determinant factor. Another hypothesis to explain our results is based on the regulatory role of endogenous and exogenous glucocorticosteroids on HPA during stress. Indeed, cortisol exerts a negative feedback on PVN, reducing CRH and AVP mediated ACTH secretion. Carlson and colleagues showed that plasma cortisol level decreased with time in CLP. It is likely that similar kinetics took place in rats with faecal peritonitis, although we were not able to measure plasma cortisol level. Because of this decrease, it is unlikely then that endogenous glucocorticoids account for neuropathological findings in septic rats, notably decreased ACTH expression. None of the rats were treated with steroids. As plasma cortisol levels were not available in patients, we are not able to assess whether it correlated with CRH, AVP and ACTH secretion. One may argue that patient who had died from septic shock would have had increased plasma cortisol level. This is controversial. If increased plasma cortisol level at onset of septic shock, was associated with mortality, few studies have assessed whether this relationship remain along the course of septi shock. It has been reported that plasma cortisol level or free cortisol level decreased with time. It has been shown no difference in the decrease with time of free cortisol level or in plasma cortisol levels before and during low–dose hydrocortisone therapy between survivors between survivors and non survivors from multitrauma, sepsis or septic shock. We recently reported that plasma cortisol levels after 10 days in average from admission were higher in patients who will die than survive from severe critical illness. It is therefore difficult to figure the relationships between plasma cortisol level and mortality along the course of the septic shock, the hypotheses that death is associated with high or low levels being both plausible. Once again, small number of patients treated with steroids precludes to asssess their correlation with neuropathological findings. The role of iNOS on neuroendocrine modulation of axis is well recognized and his expression may contribute to stunting of HPA in sepsis. Most experimental studies reported that nitric oxide stimulates the expression of CRH and suppresses the stimulatory effect of AVP on ACTH secretion.