Enhanced airway inflammation and decreased subepithelial fibrosis in interleukin 6-deficient mice following chronic exposure to aerosolized antigen.

Background: Airway inflammation and remodelling are characteristic features of chronic asthma.

Objective: To elucidate the role of interleukin (IL)-6 in airway responses to chronic antigen exposure.

Methods: We compared airway inflammation, subepithelial collagen deposition, cytokine mRNA expression, and airway responsiveness between IL-6-deficient and wild-type (WT) mice following sensitization and repeated exposure to ovalbumin (OVA) three times a week for 8 weeks.

Results: The repeated exposure to OVA induced infiltration of eosinophils, neutrophils, and lymphocytes into the airway, and caused thickening of the basement membrane and subepithelial fibrosis. IL-6-deficient mice exhibited more pronounced infiltration of these cells, a thinner basement membrane, and decreased subepithelial fibrosis, compared with WT mice. The repeated OVA exposure increased expression of IL-4, IL-13, eotaxin, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 mRNA in WT mice. Among these factors, expression of IL-13 and MCP-1 mRNA was further enhanced in IL-6-deficient mice, compared with WT mice. However, both WT and IL-6-deficient mice exhibited similar levels of airway responsiveness to increasing doses of methacholine, even after repeated exposure to OVA.

Conclusion: These results suggest that IL-6 has dual roles in the chronic phase of asthma: down-regulation of inflammatory cell infiltration and enhancement of airway remodelling.