Surgical trauma and immunosuppression: pathophysiology and potential immunomodulatory approaches.
BACKGROUND
Several studies indicate that organ failure is the leading cause of death in the postoperative phase after major surgery. An excessive inflammatory response followed by a dramatic depression of cell-mediated immunity after major surgery appears to be responsible for the increased susceptibility to subsequent sepsis. In view of this, most of the scientific and medical research has been directed towards measuring the progression and interrelationship of mediators after major surgery. Furthermore, the effect of those mediators on cell-mediated immune responses has been studied.


OBJECTIVE
This article focuses on the effect of surgical injury and blood loss on cell-mediated immune responses in experimental studies utilizing models of trauma and hemorrhagic shock. The findings from those experimental studies will also be correlated with data from surgical patients.


RESULTS
Recently, a gender-dimorphic immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis has been found. Androgens have been shown to be responsible for the immunosuppression after trauma-hemorrhage in males. In contrast, female sex steroids exhibit immunoprotective properties after trauma and severe blood loss.


CONCLUSIONS
In view of these findings, clinically relevant therapeutic strategies have been developed using the testosterone receptor blocker flutamide and/or estrogen or agents with estrogenic effects, i.e., dehydroepiandrosterone, which might yield safe and useful therapeutic approaches for the treatment of immune depression in surgical patients.
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Martin K
MK
Angele
Irshad H
IH
Chaudry
D016063:Blood Loss, Surgical / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009102:Multiple Organ Failure / Q000276:immunology; D018805:Sepsis / Q000276:immunology; D012737:Sex Factors; D012771:Shock, Hemorrhagic / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology* / Q000503:physiopathology
D007155:Immunologic Factors; D018836:Inflammation Mediators