PMID- 15298576 OWN - NLM STAT- MEDLINE DCOM- 20041220 LR - 20061115 IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 34 IP - 8 DP - 2004 Aug TI - Enhanced airway inflammation and decreased subepithelial fibrosis in interleukin 6-deficient mice following chronic exposure to aerosolized antigen. PG - 1321-8 AB - 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. FAU - Qiu, Z AU - Qiu Z AD - Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, Kanazawa, Japan. FAU - Fujimura, M AU - Fujimura M FAU - Kurashima, K AU - Kurashima K FAU - Nakao, S AU - Nakao S FAU - Mukaida, N AU - Mukaida N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (Aerosols) RN - 0 (Allergens) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Growth Substances) RN - 0 (Interleukin-6) RN - 9006-59-1 (Ovalbumin) RN - 9007-34-5 (Collagen) SB - IM MH - Aerosols MH - Allergens/*administration & dosage MH - Animals MH - Asthma/*immunology/pathology MH - Bronchoalveolar Lavage Fluid/cytology MH - Cell Count MH - Chemokines/analysis MH - Chronic Disease MH - Collagen/analysis MH - Cytokines/analysis MH - Female MH - Fibrosis MH - Growth Substances/analysis MH - Interleukin-6/genetics/*immunology MH - Lung/*immunology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Knockout MH - Models, Animal MH - Ovalbumin EDAT- 2004/08/10 05:00 MHDA- 2004/12/21 09:00 CRDT- 2004/08/10 05:00 PHST- 2004/08/10 05:00 [pubmed] PHST- 2004/12/21 09:00 [medline] PHST- 2004/08/10 05:00 [entrez] AID - CEA2013 [pii] AID - 10.1111/j.1365-2222.2004.02013.x [doi] PST - ppublish SO - Clin Exp Allergy. 2004 Aug;34(8):1321-8. doi: 10.1111/j.1365-2222.2004.02013.x.