RESUMEN
Endothelin is produced by injured or ischemic endothelium and causes monocyte production of interleukins-6 and 8 in vitro. Endothelin levels increase in patients with burn injuries, and we asked whether interleukin-6 and 8 levels increased in patients with burn injuries concurrently with endothelin. Fourteen patients with more than 20% body surface area burns were resuscitated to maintain urine output of 0.5 to 1.0 ml/kg/hr. Blood was drawn on admission and at 12, 24, and 48 hours. Endothelin was measured by radioimmunoassay, interleukins-6 and 8 were measured by enzyme-linked immunosorbent assay. Endothelin levels increased to 6.1 +/- 2.3 fmol on admission, 5.7 +/- 2.1 at 12 hours, 6.9 +/- 2.7 at 24 hours, and 6.4 +/- 2.7 at 48 hours (vs 0.5 in healthy controls). Interleukin-6 increased to 243 +/- 220 pg/ml on admission, 276 +/- 198 at 12 hours, 400 +/- 282 at 24 hours, and 379 +/- 274 at 48 hours (vs less than 50 in healthy controls). Interleukin-8 increased to 504 +/- 309 pg/ml on admission, 483 +/- 263 at 12 hours, 575 +/- 306 at 24 hours, and 698 +/- 667 at 48 hours (vs less than 50 in controls). Endothelin-1 and interleukin-6 and 8 levels increase in patients with burn injuries. Endothelin-mediated activation of monocytes that cause cytokine production may have clinical relevance in patients with burn injuries.
Asunto(s)
Quemaduras/metabolismo , Endotelina-1/análisis , Interleucina-6/análisis , Interleucina-8/análisis , Adulto , Anciano , Análisis de Varianza , Quemaduras/patología , Endotelina-1/metabolismo , Humanos , Puntaje de Gravedad del Traumatismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Persona de Mediana Edad , Pronóstico , Radioinmunoensayo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Endothelin-1 (ET-1), a powerful vasoconstrictor, is a 21 amino acid peptide produced by endothelium. It negatively affects pulmonary, cardiac, hepatic, and renal function. It also constricts bronchial and gut smooth muscle. This peptide also stimulates monocytes to produce prostaglandin E2 (PGE2), tumor necrosis factor, interleukin-6 and 8, and substances that stimulate neutrophil superoxide production. Plasma levels of ET-1 also increase in shock, low flow states, ischemia, and sepsis. STUDY DESIGN: Fourteen patients between the ages of seven and 72 years were admitted to the Bridgeport Hospital Burn Unit and resuscitated with a modified Parkland formula. Plasma was drawn on admission, at 12, 24, and 48 hours. Endothelin-1 and PGE2 were measured by radioimmunoassay. RESULTS: Endothelin-1 levels increased ten- to 20-fold in all patients. Prostaglandin E2 levels increased five- to 40-fold in all patients. There was no correlation between plasma ET-1 or PGE2 levels with either size of burn, inhalation injury, patient age, organ dysfunction, or survival in this small study of early burn injury. CONCLUSIONS: The increased plasma ET-1 response in patients with burns may have a role in the genesis of the systemic response to burns. This peptide may also activate monocyte production of PGE2 and other mediators of the systemic inflammatory response syndrome. This study was done to measure ET-1 and PGE2 levels in patients with burns greater than 20 percent of the body surface area on admission, at 12, 24, and 48 hours. The correlations between severity of burn, ET-1 levels, and PGE2 production were also assessed.
Asunto(s)
Quemaduras/sangre , Dinoprostona/sangre , Endotelinas/sangre , Adolescente , Adulto , Factores de Edad , Anciano , Presión Sanguínea/fisiología , Superficie Corporal , Quemaduras/patología , Quemaduras/fisiopatología , Quemaduras/orina , Quemaduras por Inhalación/sangre , Niño , Humanos , Persona de Mediana Edad , Monocitos/metabolismo , Tasa de Supervivencia , Factores de TiempoRESUMEN
Endothelin is a peptide with 21 amino acids that is produced by ischemic or injured endothelial cells. As indicated by in vitro and animal studies, endothelin is also a potent constrictor for renal mesangial and coronary vessels, a bronchoconstrictor, and an endocrine regulator. Our laboratory has shown that endothelin is an agonist for monocyte production of interleukins-1, -6, and -8, prostaglandin E2, and substances that trigger superoxide production. Systemic endothelin levels increase in patients with hypoperfusion and sepsis, indicating that endothelin may be yet another important cytokine in critical illness. Though endothelin has been shown to be a potent vasoconstrictor in healthy dogs, systemic vascular resistance does not increase in critically ill patients with high endothelin levels. (We hypothesize that this might be due to prostaglandin E2-mediated vasodilation predominating over endothelin-mediated vasoconstriction.) We questioned whether any changes occur in systemic endothelin levels in patients with major burns (> 20%). Ten hemodynamically stable patients resuscitated by a modified Parkland formula to a urine output greater than 30 ml/hr had endothelin levels drawn on admission and at 1, 6, 12, 24, and 48 hours after admission. Endothelin levels were measured by radioimmunoassay. Mean endothelin levels were elevated at 205 +/- 28 fmol/ml at all time points in contrast to levels of 39 +/- 9 fmol/ml in the healthy control group. In summary, systemic endothelin levels increase significantly in patients with major burns. Endothelin may be yet another cytokine playing a significant role in the immune, inflammatory, and multiorgan dysfunction observed with major burns.