Burn injury enhances alveolar macrophage endotoxin sensitivity

Systemic activation of inflammatory cascades has been implicated in the pathogenesis of the multiple organ dysfunction syndrome. To begin to determine whether dysregulation of macrophage cytokine expression after burn plays a role in organ failure, we examined tumor necrosis factor alpha bioactivity of liver and lung macrophages under two conditions: (1) at 1, 3, 5, and 7 days after 40% scald burn, and (2) after sequential insult consisting of 40% scald burn followed by in vitro incubation with endotoxin. Burn alone did not significantly alter alveolar macrophage or Kupffer cell tumor necrosis factor alpha bioactivity at any of the timepoints examined. Sequential insult did not result in significant changes in Kupffer cell tumor necrosis factor alpha, but tumor necrosis factor alpha was increased 11.1 times in alveolar macrophages harvested on postburn day 3. Therefore macrophage cytokine responses to thermal injury are apparently both tissue-specific and time-dependent.