Capacity of glycine to modulate early inflammatory disturbances after serious gunshot injuries in the pig.
OBJECTIVE
Perturbation of immune homeostasis is an important determinant for organ dysfunction following multiple injuries. The aim of this study was to investigate the ability of glycine to influence the immediate post-traumatic inflammatory environment and altered reactivity of circulating leucocytes.


METHODS
Twenty pigs were subjected to two standardized gunshots to the abdomen and thigh. Treatment was started immediately. The animals were randomized to receive either glycine 180 mg/kg i.v. over 30 min (n=10) or normal saline (n=10). Blood samples were drawn at baseline and 75 min after injury. In a follow-up study 12 pigs were exposed to an identical trauma. Blood was drawn at the same time-points and stimulated with lipopolysaccharide (LPS) or LPS plus glycine for 2 h in an ex vivo whole blood model.


RESULTS
Selected physiologic variables and organ injury did not differ between groups 75 min after trauma. Reactive oxygen species decreased to 82.7+/-5.5 % of baseline (p<0.05) in the glycine group (unaltered in the controls). Liver glutathione concentrations decreased in parallel in both groups. In vivo production of TNF-alpha and IL-1-beta increased to the same extent regardless of treatment. Trauma induced a strong LPS tolerance. In whole blood challenged with LPS, glycine inhibited cytokine synthesis, but only in samples drawn at baseline.


CONCLUSIONS
Post-traumatic infusion of glycine only modestly influenced the early post-traumatic inflammatory environment. Our ex vivo results confirm previous reports on the anti-inflammatory potential of glycine, but restricted to pre-trauma conditions.
Gundersen
Y
Y
Norwegian Defence Research Establishment, Division of Protection, Kjeller, Norway. yngvar.gundersen@ffi.no
Vaagenes
P
P
Os
Ø
Ø
Pillgram-Larsen
J
J
Sundnes
K O
KO
Opstad
P K
PK
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology / Q000627:therapeutic use*; D018684:Glycine Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000502:physiology; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D023421:Models, Animal; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D014948:Wounds, Gunshot / Q000150:complications / Q000188:drug therapy* / Q000276:immunology
D016207:Cytokines; D018684:Glycine Agents; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D005978:Glutathione; D005998:Glycine