Elucidating the role of interleukin 1beta and prostaglandin E2 in upper airway mucosal wound healing.

OBJECTIVES: To determine whether (1) inflammatory mediators IL-1beta (interleukin 1beta) and prostaglandin E2 (PGE2) in mucosal secretions correlate with subglottic mucosal injury; and (2) mucosal fibroblasts contribute to PGE2 production during mucosal healing.
DESIGN: The subglottic mucosa in rabbits was wounded by means of varied carbon dioxide laser power and duration. Subglottic fibroblasts were exposed to IL-1beta and assayed for production of PGE2.
SUBJECTS: Thirty-eight New Zealand white rabbits were used. Fibroblasts from normal and pathologic human subglottic tissues were grown in culture.
INTERVENTIONS: Subglottic injury was established in 29 rabbits, and 9 rabbits were sham-wounded. Subglottic mucosal secretions were collected at baseline and days 1, 3, 7, 14, and 21 postoperatively and assayed for IL-1beta and PGE2 by enzyme-linked immunosorbent assay. Tissue was analyzed using quantitative polymerase chain reaction. Fibroblast cultures were exposed to IL-1beta and analyzed for PGE2 and its synthetic enzymes.
RESULTS: Subglottic injury was associated with increased levels of IL-1beta and PGE2 in secretions. More extensive mucosal injury resulted in higher PGE2 levels at earlier times. Levels of IL-1beta were maximal after lesser damage. Expression of IL-beta and cyclo-oxygenase 2 was elevated after mucosal injury. Fibroblast treatment with IL-1beta resulted in translocation of nuclear factor kappaB, up-regulation of PGE2 synthetic enzymes, and increased production of endogenous PGE2.
CONCLUSIONS: Mucosal injury is associated with up-regulation of inflammatory genes and parallel increases in secretion levels of IL-1beta and PGE2, key mediators of inflammation and healing. Subglottic mucosal fibroblasts are a potential source of inflammatory mediators after injury or other trauma.