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 on set of hemorrhage. Furthermore, endothelial cell dysfunction occurs after t rauma-hemorrhage and may contribute to alterations in immune function. Rece nt studies have shown that administration of L-arginine restores the depres sed organ blood flow, probably because of the provision of substrate for co nstitutive nitric oxide synthase. It remains unknown, however, whether admi nistration of L-arginine would have any salutary effect on the depressed ma crophage 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 pressu re of 40 mm Hg until 40% of the maximum shed blood volume was returned in t he form of lactated Ringer's solution. Sham-operated rats underwent both fe moral artery cannulation and ligation, but these animals were neither bled nor resuscitated. Hemorrhaged rats were then resuscitated with lactated Rin ger's solution, receiving four times the maximum shed blood volume over 1 h our. During resuscitation, one group received 300 mg/kg L-arginine and the other group received;saline (vehicle) intravenously, At 4 hours after resus citation, 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 s ignificantly decreased in trauma-hemorrhage vehicle-treated rats. Administr ation of L-arginine after trauma-hemorrhage, however, improved splenic and peritoneal macrophage IL-1 beta and IL-6 release. Moreover, the up-regulate d 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 i ncreased plasma IL-6 levels and improving organ blood flow. Early enhanceme nt of the depressed constitutive nitric ox;ide synthase activity by provisi on of L-arginine after trauma-hemorrhage, therefore, represents a novel and safe approach for improving the depressed immune function and decreasing p lasma IL-6 levels under such conditions.