Targeting the gut to prevent sepsis from a cutaneous burn
Fatemeh Adiliaghdam, Paul Cavallaro, Vidisha Mohad, Marianna Almpani, Florian Kühn, Mohammad Hadi Gharedaghi, Mehran Najibi, Laurence G. Rahme, Richard A. Hodin
Fatemeh Adiliaghdam, Paul Cavallaro, Vidisha Mohad, Marianna Almpani, Florian Kühn, Mohammad Hadi Gharedaghi, Mehran Najibi, Laurence G. Rahme, Richard A. Hodin
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Research Article Gastroenterology Microbiology

Targeting the gut to prevent sepsis from a cutaneous burn

Abstract

Severe burn injury induces gut barrier dysfunction and subsequently a profound systemic inflammatory response. In the present study, we examined the role of the small intestinal brush border enzyme, intestinal alkaline phosphatase (IAP), in preserving gut barrier function and preventing systemic inflammation after burn wound infection in mice. Mice were subjected to a 30% total body surface area dorsal burn with or without intradermal injection of Pseudomonas aeruginosa. Mice were gavaged with 2000 units of IAP or vehicle at 3 and 12 hours after the insult. We found that both endogenously produced and exogenously supplemented IAP significantly reduced gut barrier damage, decreased bacterial translocation to the systemic organs, attenuated systemic inflammation, and improved survival in this burn wound infection model. IAP attenuated liver inflammation and reduced the proinflammatory characteristics of portal serum. Furthermore, we found that intestinal luminal contents of burn wound–infected mice negatively impacted the intestinal epithelial integrity compared with luminal contents of control mice and that IAP supplementation preserved monolayer integrity. These results indicate that oral IAP therapy may represent an approach to preserving gut barrier function, blocking proinflammatory triggers from entering the portal system, preventing gut-induced systemic inflammation, and improving survival after severe burn injuries.

Authors

Fatemeh Adiliaghdam, Paul Cavallaro, Vidisha Mohad, Marianna Almpani, Florian Kühn, Mohammad Hadi Gharedaghi, Mehran Najibi, Laurence G. Rahme, Richard A. Hodin

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Figure 3

IAP supplementation diminishes burn site infection–induced systemic inflammation and improves survival.

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IAP supplementation diminishes burn site infection–induced systemic infl...
(A) Bacterial burden in mesenteric lymph nodes (MLNs) of mice that underwent sham procedure (black bar), burn wound infection treated with vehicle (red bar), or burn wound infection treated with IAP (blue bar), expressed as log of colony-forming units (CFUs) normalized by tissue weight. (B) Bacterial burden in systemic blood expressed as log of CFUs normalized by blood volume. (C) Serum endotoxin level measured by Limulus amebocyte lysate assay. (D) TNF-α levels in the serum measured by ELISA. (E) Survival in sham vs. burn wound–infected mice treated with vehicle or IAP. (** above the blue line denote the difference between the vehicle and the IAP supplementation group, whereas *** above the red line denote the difference between the sham and the IAP supplementation group). One-way ANOVA with multiple post hoc comparisons using Tukey’s test was performed. Kaplan-Meier survival analysis curve was used for the survival study, and the groups were compared using the log-rank test. Each group included 5 animals and data are representative of 3 biological replicates. The survival study includes 14 burn site–infected and 13 burn site–infected IAP-treated mice. **P < 0.01, ***P < 0.001, ****P < 0.0001. IAP, intestinal alkaline phosphatase.