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Updated: Aug 6, 2026
Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock
Published on: June 6, 2011
Hemorrhage decreases macrophage inflammatory protein 2 and interleukin-6 release: a possible mechanism for increased
M K Angele1, M W Knöferl, M G Schwacha
1Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Objective:
To determine whether alteration in wound exudate cell immune function occurs after trauma-hemorrhage.
Background:
Although clinical and experimental studies indicate that the rate of wound infection is increased after trauma and hemorrhagic shock, the underlying mechanism for this increased susceptibility remains unknown.
Methods:
Male C3H/HeN mice were subjected to a midline laparotomy and polyvinyl alcohol sponges were implanted subcutaneously in the abdominal wound before hemorrhage (35+/-5 mm Hg for 90 minutes and resuscitation) or sham operation. The wound exudate cells from the sponges were harvested on the first, third, and fifth postoperative day and cultured for 24 hours in the presence of lipopolysaccharide (10 microg/ml) or heat-killed Staphylococcus aureus. Interleukin (IL)-1beta, IL-6, monocyte chemotactic protein 1, macrophage inflammatory protein 2, and nitrite levels were determined in the supernatants. The distribution of macrophages and polymorphonuclear leukocytes was assessed in the sponge with and without in vivo injection of S. aureus. The phagocytic activity of isolated wound exudate cells was determined using fluorescent S. aureus.
Results:
The composition of exudate cells was unaltered by hemorrhagic shock; however, in vivo injection of S. aureus significantly decreased the percentage of macrophages under such conditions. Wound exudate cell phagocytic activity and the release of IL-1beta, IL-6, monocyte chemotactic protein 1, and macrophage inflammatory protein 2 was decreased on the first postoperative day. The release of IL-1beta and IL-6 was also decreased on the third postoperative day in hemorrhaged mice. On the fifth postoperative day, wound exudate cell cytokine production was comparable to that in shams.
Conclusions:
Because most wound infections occur early after severe trauma, these results suggest that the dysfunction of wound exudate cells after hemorrhage might contribute to the increased incidence of wound infections. Therefore, attempts to enhance or restore wound cell immune function might be helpful for decreasing the incidence of wound infections in trauma victims.
Insights
Trauma-hemorrhage impairs wound exudate cell immune function, decreasing phagocytosis and cytokine release. This dysfunction may explain increased wound infection rates after severe trauma.
Area of Science:
- Immunology
- Trauma research
- Wound healing
Background:
- Increased wound infection rates are observed after trauma and hemorrhagic shock.
- The precise mechanisms underlying this heightened susceptibility to infection remain unclear.
Purpose of the Study:
- To investigate alterations in wound exudate cell immune function following trauma-hemorrhage.
- To identify potential mechanisms contributing to increased infection risk in trauma patients.
Main Methods:
- Mice underwent laparotomy and sponge implantation, followed by hemorrhage or sham operation.
- Wound exudate cells were harvested and stimulated to assess immune responses, including cytokine release and phagocytic activity.
- Cellular composition and distribution were analyzed in response to bacterial challenge.
Main Results:
- Hemorrhagic shock did not alter the basic composition of wound exudate cells but impaired their function.
- Phagocytic activity and the release of key inflammatory cytokines (IL-1beta, IL-6) were significantly reduced post-hemorrhage, particularly on days 1 and 3.
- Immune cell function largely recovered by day 5, suggesting a transient but critical period of impairment.
Conclusions:
- Dysfunctional wound exudate cells following hemorrhage likely contribute to the increased incidence of early-onset wound infections.
- Strategies aimed at enhancing or restoring immune cell function in wound sites could be beneficial in preventing infections in trauma victims.
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