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The effect of severe burn injury on proinflammatory cytokines and leukocyte behavior: its modulation with granulocyte
F W Peter1, D A Schuschke, J H Barker
1Division of Plastic and Reconstructive Surgery, University of Louisville School of Medicine, KY 40292, USA. 75473.672@CompuServe.COM
Abstract:
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.
Insights
Granulocyte-colony stimulating factor (GCSF) administration in rats with severe burns increased white blood cell and neutrophil counts. GCSF helped restore immune competence without overactivating leukocytes or increasing inflammation.
Area of Science:
- Immunology
- Trauma Research
- Wound Healing
Background:
- Severe injuries, such as burns, lead to immunosuppression.
- Impaired leukocyte function and cytokine imbalance are key factors in post-injury immunosuppression.
- Granulocyte-colony stimulating factor (GCSF) is known to increase neutrophil counts and modulate inflammation, but its potential to overactivate leukocytes is a concern.
Purpose of the Study:
- To investigate the efficacy of GCSF in restoring immune competence following severe injury.
- To determine if GCSF administration leads to overactivation of leukocytes.
Main Methods:
- Lewis rats were subjected to a 30% total body surface area (TBSA) burn and treated with either GCSF or a vehicle control.
- Blood samples were analyzed for total white cell count, neutrophils (PMNs), and cytokine levels (TNF-alpha, IFN-gamma).
- Leukocyte function, including rolling, sticking, and diapedesis, was assessed in vivo.
Main Results:
- GCSF treatment significantly increased total white cell and neutrophil counts compared to the vehicle group (P<0.001).
- Leukocyte adherence and diapedesis were not elevated in the GCSF group, indicating no overactivation.
- GCSF administration led to decreased levels of pro-inflammatory cytokines TNF-alpha (P<0.05) and IFN-gamma (P<0.001) compared to the vehicle group.
Conclusions:
- GCSF effectively restores immune competence after severe injury by increasing leukocyte counts.
- GCSF modulates the immune response, shifting it from a pro-inflammatory to a more balanced state.
- GCSF does not cause overactivation of neutrophils in the context of severe injury.