The effect of severe burn injury on proinflammatory cytokines and leukocyte behavior: its modulation with granulocyte colony-stimulating factor.
Severe injury causes immunosuppression. The main contributors are impaired leukocyte function and a cytokine dysbalance. GCSF increases PMN count, function and modulates the inflammatory response. However GCSF may overactivate leukocytes. The purpose of this study is to investigate whether GCSF is able to restore immune competence after severe injury. Lewis rats were divided into three groups: 30% TBSA burn + vehicle; 30% TBSA burn + GCSF (150 microg rhGCSF); Control. Blood samples were taken for total white cell count, PMNs, TNFalpha and IFNgamma. Leukocyte rolling and sticking were measured in the cremaster muscle microcirculation. Leukocyte diapedesis was investigated by lavage of the abdominal cavity and the lungs. Total white cell and PMN counts in the burn + GCSF group were significantly higher (P<0.001) than in burn+vehicle animals. Leukocyte adherence and diapedesis were not elevated in the burn + GCSF group as compared to the burn + vehicle group. TNFalpha (P<0.05) and IFNgamma (P<0.001) levels were significantly increased in the burn + vehicle animals compared to the burn + GCSF animals. GCSF modifies the immune system, as shown by an increase in white cell and PMN counts and by balancing the overall immune response from proinflammatory to normal, as shown by decreased TNFalpha and IFNgamma levels. GCSF does not overactivate PMNs.
Peter
F W
FW
Division of Plastic and Reconstructive Surgery, University of Louisville School of Medicine, KY 40292, USA. 75473.672@CompuServe.COM
Schuschke
D A
DA
Barker
J H
JH
Fleishcher-Peter
B
B
Pierangeli
S
S
Vogt
P M
PM
Steinau
H U
HU
D000005:Abdomen / Q000473:pathology; D000818:Animals; D002056:Burns / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects; D007371:Interferon-gamma / Q000097:blood* / Q000187:drug effects; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D015599:Trauma Severity Indices; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma