Differential local and systemic tumor necrosis factor-alpha responses to a second hit of lipopolysaccharide after hemorrhagic shock.
BACKGROUND
The immune response to subsequent stressors after traumatic hemorrhage and resuscitation (HR) may be dependent on timing and counterinflammatory cytokine expression. Our hypothesis was that the timing of the second hit would influence the immune response, and we investigated whether an early second stimulus after HR would result in worse acute lung injury.


METHODS
One hour after HR or sham shock (Sham), mice were given intraperitoneal (IP) injections of lipopolysaccharide (LPS) or saline (Sal). Mortality, pulmonary function (PF), bronchoalveolar lavage neutrophil infiltration, and bronchoalveolar lavage (BAL), in addition to serum interleukin (IL)-10, IL-6, and tumor necrosis factor-alpha (TNF-alpha), were assessed.


RESULTS
HR blunted serum TNF-alpha expression to LPS (HR+LPS, 424.8 pg/mL; Sham+LPS, 2,248.8 pg/mL; p < 0.05), but primed for increased bronchoalveolar lavage TNF-alpha (HR+LPS, 259.5 pg/mL; Sham+LPS, 23.5 pg/mL; p < 0.05). Elevated serum TNF-alpha corresponded with greater bronchoalveolar lavage neutrophil infiltration (HR+LPS, 0.93%; Sham+LPS, 17.5%; p < 0.05). IL-10 expression was similar in HR and Sham. There were no significant differences in mortality or PF between HR+LPS and Sham+LPS.


CONCLUSIONS
Priming and blunting of the LPS-induced TNF-alpha response occurred concomitantly in two-hit mice, corresponding to an altered pattern of pulmonary inflammation, but no change in PF.
Schulman
Andrew M
AM
Trauma Research Laboratory, University of Virginia Health System, Charlottesville, 22908, USA.
Claridge
Jeffrey A
JA
Ghezel-Ayagh
Anousheh
A
Johnson
Owen
O
Young
Jeffrey S
JS
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis*; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000209:etiology / Q000628:therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000970:Antineoplastic Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10