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.


CONCLUSIONS
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.
Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, Kanazawa, Japan.
Z
Z
Qiu
M
M
Fujimura
K
K
Kurashima
S
S
Nakao
N
N
Mukaida
D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000032:analysis; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D005260:Female; D005355:Fibrosis; D006133:Growth Substances / Q000032:analysis; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D010047:Ovalbumin
D000336:Aerosols; D000485:Allergens; D018925:Chemokines; D016207:Cytokines; D006133:Growth Substances; D015850:Interleukin-6; D010047:Ovalbumin; D003094:Collagen