Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model.
OBJECTIVE
We previously showed that topical inhibition of inflammatory signaling in burn wounds reduced systemic inflammatory response and burn-induced pulmonary inflammation. We hypothesized that this topical intervention would attenuate burn-induced lung injury, improve pulmonary function, protect lungs from bacterial invasion, and reduce mortality.


METHODS
Controlled, in vivo, laboratory study.


METHODS
University laboratory.


METHODS
Female mice, 8-10 wks old.


METHODS
Animals received 30% total body surface area burn followed by topical application of a specific inhibitor of p38 mitogen-activated protein kinase, a key inflammatory signaling pathway, or vehicle to the wound. Twenty-four hours after injury, pulmonary collagen deposition and pulmonary function were assessed. One day postburn, some of the animals received intratracheal instillation of Klebsiella pneumoniae and were subsequently monitored for 7 days.


RESULTS
Topical inhibition of p38 mitogen-activated protein kinase significantly decreased pulmonary collagen deposition and prevented a decline in pulmonary function at 1 day after burn injury. Compared with sham controls, animals with burn injury had a significantly higher mortality in response to intratracheal bacterial challenge. Application of p38 mitogen-activated protein kinase inhibitor to the burn wound attenuated pulmonary neutrophil infiltration and reduced the mortality rate to a level experienced by sham controls.


CONCLUSIONS
Inflammatory source control in burn wounds with topical p38 mitogen-activated protein kinase inhibition attenuates acute lung injury, avoids pulmonary dysfunction, protects lungs from bacterial challenge, and improves survival.
Ipaktchi
Kyros
K
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Mattar
Aladdein
A
Niederbichler
Andreas D
AD
Kim
Jiyoun
J
Hoesel
Laszlo M
LM
Hemmila
Mark R
MR
Su
Grace L
GL
Remick
Daniel G
DG
Wang
Stewart C
SC
Arbabi
Saman
S
D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007710:Klebsiella Infections / Q000517:prevention & control; D007711:Klebsiella pneumoniae; D008168:Lung / Q000378:metabolism; D051379:Mice; D011014:Pneumonia / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases