Differential Local and Systemic Tumor Necrosis Factor-?? 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 counterin-flammatory 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-a (TNF-a), were assessed. Results: HR blunted serum TNF-a 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-α (HR+LPS, 259.5 pg/ mL; Sham+LPS, 23.5 pg/mL; p < 0.05). Elevated serum TNF-α 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. Conclusion: Priming and blunting of the LPS-induced TNF-a response occurred concomitantly in two-hit mice, corresponding to an altered pattern of pulmonary inflammation, but no change in PF.