In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial.
<i>In vitro</i> and preclinical <i>in vivo</i> data show that administration of ADM exerts anti-inflammatory, antimicrobial, and protective effects on endothelial barrier function during sepsis, but other work suggests that it may also decrease blood pressure, which could be detrimental for patients with septic shock.
Adrenomedullin (ADM) is an important regulator of endothelial barrier function and vascular tone, and may represent a novel treatment target in sepsis.
Compared to those of healthy individuals (n = 47), mRNA levels of ANG2, IL10, HBP, PCT, and ADM were increased in patients who eventually developed sepsis.
Finally, effects of single and repeated dose administration of HAM1101, HAM8101 and placebo on survival were assessed in CLP-induced murine sepsis (n = 60, n = 10 per group).
In this review, we first provide a brief overview of the currently available data on the role of adrenomedullin in sepsis and describe its effects on endothelial barrier function and vasodilation.
The biological role of adrenomedullin (ADM), a hormone involved in hemodynamic homeostasis, is controversial in sepsis because administration of either the peptide or an antibody against it may be beneficial.
It remains unknown whether a combination of human AM and human AMBP-1 (AM/AMBP-1) is also beneficial in sepsis and, if so, whether human AM/AMBP-1 reverses established sepsis in rats.
Specifically, we find that certain conditions, such as pregnancy, cardiovascular disease, and sepsis, are associated with robust and dynamic changes in the expression of AM and AM receptor proteins, which together represent an elegant mechanism for altering the physiological responsiveness or function of AM.
Strong evidence now exists that AM is able to act as an autocrine, paracrine, or endocrine mediator in a number of biologically significant functions, including the endothelial regulation of blood pressure, protection against organ damage in sepsis or hypoxia, and the control of blood volume through the regulation of thirst.
It is revealed that the distributions of receptor or binding sites of AM are changed in sepsis, and it is suggested that AM plays distinct roles in the clinical course of this syndrome.