Pulmonary contusion primes systemic innate immunity responses.
BACKGROUND
Traumatic injury may result in an exaggerated response to subsequent immune stimuli such as nosocomial infection. This "second hit" phenomenon and molecular mechanism(s) of immune priming by traumatic lung injury, specifically, pulmonary contusion, remain unknown. We used an animal model of pulmonary contusion to determine whether the injury resulted in priming of the innate immune response and to test the hypothesis that resuscitation fluids could attenuate the primed response to a second hit.


METHODS
Male, 8 to 9 weeks, C57/BL6 mice with a pulmonary contusion were challenged by a second hit of intratracheal administration of the Toll-like receptor 4 agonist, lipopolysaccharide (LPS, 50 microg) 24 hours after injury (injury + LPS). Other experimental groups were injury + vehicle or LPS alone. A separate group was injured and resuscitated by 4 cc/kg of hypertonic saline (HTS) or Lactated Ringer's (LR) resuscitation before LPS challenge. Mice were killed 4 hours after LPS challenge and blood, bronchoalveolar lavage, and tissue were isolated and analyzed. Data were analyzed using one-way analysis of variance with Bonferroni multiple comparison posttest for significant differences (*p < or = 0.05).


RESULTS
Injury + LPS showed immune priming observed by lung injury histology and increased bronchoalveolar lavage neutrophilia, lung myeloperoxidase and serum IL-6, CXCL1, and MIP-2 levels when compared with injury + vehicle or LPS alone. After injury, resuscitation with HTS, but not Lactated Ringer's was more effective in attenuating the primed response to a second hit.


CONCLUSIONS
Pulmonary contusion primes innate immunity for an exaggerated response to a second hit with the Toll-like receptor 4 agonist, LPS. We observed synergistic increases in inflammatory mediator expression in the blood and a more severe lung injury in injured animals challenged with LPS. This priming effect was reduced when HTS was used to resuscitate the animal after lung contusion.
Hoth
J Jason
JJ
Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. jhoth@wfubmc.edu
Martin
R S
RS
Yoza
Barbara K
BK
Wells
Jonathan D
JD
Meredith
J W
JW
McCall
Charles E
CE
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000097:blood*; D054426:Chemokine CXCL2 / Q000097:blood*; D003288:Contusions / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood*; D008168:Lung / Q000201:enzymology / Q000473:pathology; D055370:Lung Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism*; D015599:Trauma Severity Indices
D015415:Biomarkers; D039481:CD11b Antigen; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D015850:Interleukin-6; D009195:Peroxidase