title: Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury.
abstract: Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, the authors examined whether therapeutic intervention with mesalamine (5-aminosalicylic acid [5-ASA]), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an approximately 20% TBSA dorsal scald burn and resuscitated with either 1 ml normal saline or 100 mg/kg of 5-ASA dissolved in saline. The authors examined intestinal transit and permeability along with the levels of small intestine epithelial cell proinflammatory cytokines and tight junction protein expression 1 day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed 1 day after burn injury, which accompanied a significant increase in gut permeability. The authors found a substantial increase in the levels of interleukin (IL)-6 (by ~1.5-fold) and IL-18 (by ~2.5-fold) in the small intestine epithelial cells 1 day after injury. Furthermore, burn injury decreases the expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn-induced increase in permeability, partially restored normal intestinal transit, normalized the levels of the proinflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin compared with that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury.
authors.affiliation: From the *Burn and Shock Trauma Research Institute, Loyola University Chicago Health Sciences Division, Maywood, Illinois; †Integrative Cell Biology Program, Loyola University Chicago Health Sciences Division, Maywood, Illinois; ‡Stritch School of Medicine, Loyola University Chicago Health Sciences Division, Maywood, Illinois; and §Department of Surgery, Loyola University Chicago Health Sciences Division, Maywood, Illinois.
authors.forename: Abigail R
authors.initials: AR
authors.lastname: Cannon
authors.forename: Suhail
authors.initials: S
authors.lastname: Akhtar
authors.forename: Adam M
authors.initials: AM
authors.lastname: Hammer
authors.forename: Niya L
authors.initials: NL
authors.lastname: Morris
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Javorski
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kennedy
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
mesh_terms: D000818:Animals; D002056:Burns / Q000628:therapy*; D062506:Claudin-4 / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000378:metabolism; D010539:Permeability
chemical_list: D062506:Claudin-4; D057167:Claudins; C568158:Cldn4 protein, mouse; D007378:Interleukins; D062793:Occludin; C568986:Ocln protein, mouse; D019804:Mesalamine; C502011:claudin 8