We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome and 13 healthy volunteers, as controls. Plasma levels of AM in SIRS (bums 20.5*3.2 fmol/ml : mean SEM ; pancreatitis 13.8*3.8 ; trauma 14.9*2.5 ; traumatic shock 41.1*7.8 ; severe sepsis 59.9*11.2 ; septic shock 193.5*30.1) were significantly elevated as compared with those in controls (5.1*0.2). Moreover, the patients with traumatic shock or septic shock showed 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 observ
ed between plasma A M and TNF-a levels in patients with septic shock, suggesting an important role for AM in the pathophysiology of inflammation as well as TNF-alpha. The plasma level of AM in patients with septic shock showed significant correlations with the values of cardiac index, stroke volume index, and heart rate, and with a decrease in diastolic blood pressure, systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI). 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 well as plasma IL-6 levels in patients with traumatic shock. Enhanced production of adrenomedullin in patients with septic shock may contribute to a reduced vascular tone and/or hypotension in septic shock. Plasma AM level might serve as a useful marker for evaluating severity and as a early predictor of subsequent organ failure and outcome in septic shock.
We demonstrated that plasma AM levels increased in patients with SIRS in proportion to its severity, suggesting that AM, endothelium derived potent vasodilator, may play an important role in the pathophysiology of inflammation. Taken together with our findings that plasma AM levels correlate with relaxation of the vascular tone in patients with septic shock, especially in septic shock AM appears to be not only a marker for evaluating severity, but also an early predictor correlating with subsequent organ dysfunction and outcome. Although further studies are needed to clarify the contribution of AM in inflammation, the regulation and modulation of the function of AM may provide us a new therapeutical strategy for patients with SIRS including septic shock.
平成10年度はseptic shock患者30名とsever e sepsis患者を16名に拡大したが,平成9年度と同様の結論を再確認した.これらのことからAMが,炎症に関与する可能性を考え,systemic inflammatory response syndrome(全身性炎症反応症候群,SIRS)で表現される疾患である熱傷,膵炎,外傷を対象疾患として拡張し,広範囲熱傷患者11名,重症膵炎患者6名,外傷患者16名,外傷性ショック患者16名を加え検討した.血漿中AM濃度は健常成人(5.2±0.2fmol/mL:mean±SEM)に比して広範囲熱傷群(20.5±3.2),重症膵炎群(13.8±3.8),外傷群(14.9±2.5),外傷性ショック群(41.1±7.8),sever e sepsis群(59.9±11.2),septic shock群(193.5±30.1)で健常成人に比して有意に上昇していた.最も上昇の低い重症膵炎群や外傷群でも高血圧や心不全および腎不全患者に匹敵もしくはそれ以上の上昇であった.また敗血症患者でsever e sepsis群に比してseptic shock群で有意に上昇していたのと同様に,外傷患者では外傷群に比して外傷性ショック群で上昇していたことから,その敗血症や外傷では重症度に応じて上昇していた.またsever e sepsis群や外傷群では血漿中AM濃度は血清クレアチニン値とは正の相関を認めたが,septic shock群や外傷性ショック群では相関を認めないことから,重症度が上昇すると排泄低下より産生亢進が血漿中AM上昇に強く関与するものと考えられた.以上から血管内皮細胞を内分泌器官とする循環調節因子であるAMが炎症に関与する可能性が指摘された. Less