L-arginine: a unique amino acid for improving depressed wound immune function following hemorrhage

Eur Surg Res. Jan-Apr 2002;34(1-2):53-60. doi: 10.1159/000048888.


Objective: To determine whether L-arginine has any salutary effects on wound immune cell function following trauma-hemorrhage.

Background: Depressed wound immune function contributes to an increased incidence of wound infections following hemorrhage. Although administration of L-arginine has been shown to restore depressed cell-mediated immune responses following hemorrhage potentially by maintaining organ blood flow, it remains unknown whether L-arginine has any salutary effects on the depressed local immune response at the wound site.

Methods: Male mice were subjected to a midline laparotomy and polyvinyl sponges were implanted subcutaneously in the abdominal wound prior to hemorrhage (35 +/- 5 mm Hg for 90 min and resuscitation) or sham operation. During resuscitation mice received 300 mg/kg body weight L-arginine or saline (vehicle). Sponges were harvested 24 h thereafter, wound fluid collected and wound immune cells cultured for 24 h in the presence of LPS. Pro- (IL-1 beta, IL-6) and anti-inflammatory (IL-10) cytokines were determined in the supernatants and the wound fluid. In addition, wounds were stained for IL-6 immunohistochemically. In a separate set of animals, skin and muscle blood flow was determined by microspheres.

Results: The capacity of wound immune cells to release IL-1 beta and IL-6 in vitro was significantly depressed in hemorrhaged mice receiving vehicle. Administration of L-arginine, however, improved wound immune cell function. In contrast, in vivo the increased IL-6 release at the wound site was decreased in L-arginine-treated mice following hemorrhage. Moreover, IL-10 levels were significantly increased in the wound fluid in hemorrhaged animals receiving L-arginine compared to vehicle-treated mice. In addition, the depressed skin and muscle blood flow after hemorrhage was restored by L-arginine.

Conclusions: Thus, L-arginine might improve local wound cell function by decreasing the inflammatory response at the wound site. Since L-arginine protected wound immune cell function this amino acid might represent a novel and useful adjunct to fluid resuscitation for decreasing wound complications following hemorrhage.

MeSH terms

  • Animals
  • Arginine / pharmacology*
  • Bacterial Infections / immunology
  • Bacterial Infections / prevention & control
  • Exudates and Transudates / chemistry
  • Exudates and Transudates / immunology
  • Interleukin-1 / analysis
  • Interleukin-1 / metabolism
  • Interleukin-10 / analysis
  • Interleukin-10 / metabolism
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C3H
  • Muscle, Skeletal / blood supply
  • Neutrophils / cytology
  • Neutrophils / metabolism
  • Regional Blood Flow / immunology
  • Shock, Hemorrhagic / immunology*
  • Skin / blood supply
  • Wound Healing / drug effects*
  • Wound Healing / immunology
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / immunology*


  • Interleukin-1
  • Interleukin-6
  • Interleukin-10
  • Arginine