Increased Plasma Levels of Adrenomedullin in Patients with Systemic Inflammatory Response Syndrome

Abstract

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

“…Systemic inflammation and sepsis leads to an increased release of ADM into circulation [124,125] , but a short half-life and other difficulties in the measurement impede the clinical use [126] .…”

Proadrenomedullin as a prognostic marker in neonatal sepsis

“…Pro-ADM (pro-ADM), a more stable precursor molecule to ADM, was reported to correlate well with other markers such as IL-6 and CRP as a predictor of prognosis in patients with sepsis (10). Elevations of pro-ADM have been reported in systemic inflammatory response syndrome (SIRS), sepsis, and septic shock in adults (11,12).…”

Adrenomedullin Reduces Endothelial Hyperpermeability

“…8,9 Accumulating evidence suggests a pivotal role of adrenomedullin (ADM), a multifunctional regulatory peptide, in sepsis and septic shock. [15][16][17][18][19] ADM, a 52-amino-acid peptide Original …”

“…8,9 Accumulating evidence suggests a pivotal role of adrenomedullin (ADM), a multifunctional regulatory peptide, in sepsis and septic shock. [15][16][17][18][19] ADM, a 52-amino-acid peptide belonging to the calcitonin gene-related peptide family, participates in the control of central body functions, such as vascular tone regulation or fluid and electrolyte homeostasis (see reviews 20,21 ). In systemic inflammatory response, plasma levels of ADM in vertebrates, including human beings, were found to be elevated.…”

“…In systemic inflammatory response, plasma levels of ADM in vertebrates, including human beings, were found to be elevated. 15,[17][18][19] Endothelial cells produce ADM in response to proinflammatory cytokines or lipopolysaccaride 22 under the control of the transcription factors nuclear factor for interleukin-6 and activator protein 2. 22 Calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP)2 and RAMP3 together form ADM receptors coupled to cholera toxin-sensitive G proteins; however, alternative ADM binding receptors may exist.…”