L-arginine: A unique amino acid for restoring the depressed macrophage functions after trauma-hemorrhage

Background: Immune responses are markedly depressed very early after the onset of hemorrhage. Furthermore, endothelial cell dysfunction occurs after trauma-hemorrhage and may contribute to alterations in immune function. Recent studies have shown that administration of L-arginine restores the depressed organ blood flow, probably because of the provision of substrate for constitutive nitric oxide synthase. It remains unknown, however, whether administration of L-arginine would have any salutary effect on the depressed macrophage function after trauma-hemorrhage. Methods: Male rats underwent midline laparotomy (i.e., trauma was induced). After this, the animals were bled to and maintained at a mean blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Sham-operated rats underwent both femoral artery cannulation and ligation, but these animals were neither bled nor resuscitated. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, receiving four times the maximum shed blood volume over 1 hour. During resuscitation, one group received 300 mg/kg L-arginine and the other group received;saline (vehicle) intravenously, At 4 hours after resuscitation, splenic and peritoneal macrophage interleukin (IL)-1 beta and IL-6 release as well as plasma IL-6 were measured. Results: Splenic and peritoneal macrophage IL-1 beta and IL-6 release was significantly decreased in trauma-hemorrhage vehicle-treated rats. Administration of L-arginine after trauma-hemorrhage, however, improved splenic and peritoneal macrophage IL-1 beta and IL-6 release. Moreover, the up-regulated plasma levels of IL-6 were attenuated by L-arginine administration. Conclusion: L-Arginine administration after trauma-hemorrhage significantly improves the depressed macrophage function, presumably by decreasing the increased plasma IL-6 levels and improving organ blood flow. Early enhancement of the depressed constitutive nitric ox;ide synthase activity by provision of L-arginine after trauma-hemorrhage, therefore, represents a novel and safe approach for improving the depressed immune function and decreasing plasma IL-6 levels under such conditions.