敗血症におけるadrenomedullinの意義

Abstract

The author measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 12 patients with severe sepsis and 27 patients with septic shock, with 13 healthy volunteers as controls. Plasma levels of AM in sepsis (severe sepsis 48.3±12.1 fmol/mL ; septic shock, 203.5±32.8) were significantly elevated as compared with those in controls (5.1±0.2). The patients with septic shock showed higher levels of plasma AM than those with severe sepsis. Subsequently, we measured the plasma levels of some mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1 and thrombomodulin (TM) in patients with severe sepsis and septic shock to compare with severity of illness. Plasma levels of AM and TNF-α in septic shock correlated with hemodynamic variables characterized hyperdynamic state. Plasma AM, TNF-α and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE)-Ⅱ score, multiple organ failure score. Plasma AM, IL-8 and PAI-1 levels correlated with prognosis. These observations suggest that plasma AM level might serve as a useful marker of severity in septic shock. Furthermore, we examined mononuclear cells derived from four septic patients for the expression of AM messenger RNA (mRNA) by using the reverse transcription-polymerase chain reaction method. AM mRNA was expressed in the mononuclear cells from septic patients, but not in those from healthy subjects, suggesting that mononuclear cells costitute one of the sources to elevate plasma AM level in sepsis. These data showed that AM may play an important role in the pathophysiology of sepsis.