Centrally, SDF-1�� can autoregulate AVP release through its receptor (CXCR4) [12,40]. Systemically, SDF-1�� is released in bloodstream early after critical illness initiation, and is associated with endothelial progenitor cell mobilization, sepsis-induced organ dysfunctions [41,42]. Indeed, in this study, blood SDF-1�� discriminated sepsis, as well as sepsis severity and outcome. A significant association was also found between blood SDF-1�� and cortisol baseline, and clusters of CXCR4-expressing cells scattered were observed within the adrenal corticosteroid productive area. This suggests the existence of a peripheral cross-talk between SDF-1��, CXCR4 (also alternative receptor to CD74 for MIF [43]) and the HPA corticotroph axis. Apelin (APL) is another counterpartner peptide with centrally-driven regulatory activities on AVP and ACTH release, and peripherally-driven diuretic and non-ACTH-dependent cortisol release effects [9,11]. In this cohort of patients, blood APL was modestly elevated in critical illness, especially in sepsis, with no evidence of correlations found with either severity or outcome, nor with corticotroph HPA axis components.Copeptin was also a more reliable diagnostic marker of sepsis than AVP in this study, as it was described as predictive of severity and outcome with more sustained blood levels than AVP in earlier works [12-16]. On the other hand, AVP was closely associated with cortisol baseline in our study, but only in non-septic ICU patients, further suggesting distinctive stress pathways in sepsis. Of note, higher blood AVP in septic shock has been observed with glucocorticoid administration [44] and a blunted cortisol response to corticotropin [45]. Also, a combination of glucocorticoids and AVP treatments was associated with improved survival and increased vasopressor-free days [44,46,47], as well as with reversal of AVP hyporesponsiveness in sheep [47]. This suggests a possible reset of sepsis-induced vascular V1aR down-regulation through the GRE receptor gene [48,49], and resurfaces a complex and often questioned link between AVP and corticosteroids, which is essentially disturbed in critical illness.A neurocorticotropic marker combination for sepsis diagnosis in acute stress after ICU admissionProcalcitonin (PCT) is a known biochemical reference marker of sepsis diagnosis and severity [13,50,51], and sepsis score is a tentative summation of clinical and biochemical variables (including PCT) [18]. However, using the cutoff recommended by the manufacturer, PCT was not a perfect biomarker, as well as sepsis score, on diagnostic prediction.