L-arginine: a unique amino acid for improving depressed wound immune function following hemorrhage.
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.
Angele
Martin K
MK
Department of Surgery, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany. manglel@aol.com
Nitsch
Stefan M
SM
Hatz
Rudolf A
RA
Angele
Peter
P
Hernandez-Richter
Thomas
T
Wichmann
Mathias W
MW
Chaudry
Irshad H
IH
Schildberg
Fredrich W
FW
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001424:Bacterial Infections / Q000276:immunology / Q000517:prevention & control; D005122:Exudates and Transudates / Q000737:chemistry / Q000276:immunology; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000098:blood supply; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D012039:Regional Blood Flow / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000276:immunology*; D012867:Skin / Q000098:blood supply; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000276:immunology*
D007375:Interleukin-1; D015850:Interleukin-6; D016753:Interleukin-10; D001120:Arginine