Injury induces localized airway increases in pro-inflammatory cytokines in humans and mice

Abstract

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)-α, interleukin (IL)-1β, 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-α, IL-1β, 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-α, IL-1β, 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-α, IL-1β, and IL-6 without significant changes in serum TNF-α or IL-1β. Serum IL-6 increased significantly.

Conclusions: Injury significantly increases human and mouse airway TNF-α, IL-1β, and IL-6. Increases are greater in the airway than in serum, implying a local rather than a systemic stress response to injury.

FIG. 1.

Human cytokine response to trauma. (A) Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in bronchoalveolar fluid in trauma group were elevated significantly compared with control group (expressed as pg/mL of epithelial lining fluid [ELF]). (B) Serum concentrations of TNF-α, IL-1β, and IL-6 in trauma group were elevated significantly compared with control group (expressed as pg/mL).

FIG. 2.

Murine cytokine response to trauma. (A) Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were increased significantly in the bronchoalveolar fluid of injured mice compared with uninjured controls (expressed as pg/mL of total BAL fluid). (B) Serum concentration of IL-6 increased significantly after injury compared with control, whereas TNF-α did not change and IL-1β remained nondetectable (expressed as pg/mL).