Injury Induces Localized Airway Increases in Pro-Inflammatory Cytokines in Humans and Mice

Background: Secretory immunoglobulin A (sIgA) increases in the airways of humans and mice after injury to protect against infection. The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 are linked molecularly to sIgA production and secretion and are required for sIgA increases in the airway after injury in a mouse model. We investigated the injury effect on airway and serum concentrations to determine the source of the cytokines involved in the airway IgA response. Methods: In the first experiment, TNF-alpha, IL-1 beta, and IL-6 concentrations in bronchoalveolar lavage (BAL) fluid and serum obtained from 11 ventilated trauma patients within 30 h of admission were compared with those in eight elective surgical patients. In the second experiment, male ICR mice received no injury (n=7) or injury with sham celiotomy and neck incisions (n=8) with sacrifice of all animals at 8 h for BAL fluid and serum cytokine measurements by enzyme-linked immunosorbent assay. Results: Injured patients had significantly higher BAL fluid and serum TNF-alpha, IL-1 beta, and IL-6 concentrations, with greater increases in the BAL fluid than in the serum. Injured mice had significantly increased BAL fluid concentrations of TNF-alpha, IL-1 beta, and IL-6 without significant changes in serum TNF-alpha or IL-1 beta. Serum IL-6 increased significantly. Conclusions: Injury significantly increases human and mouse airway TNF-alpha, IL-1 beta, and IL-6. Increases are greater in the airway than in serum, implying a local rather than a systemic stress response to injury.