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Neutralization of both IL-1α/IL-1ß plays a major role in suppressing combined cigarette smoke/virus-induced pulmonary inflammation in mice.
Bucher, Hannes; Mang, Samuel; Keck, Martina; Przibilla, Michèl; Lamb, David J; Schiele, Felix; Wittenbrink, Mareike; Fuchs, Klaus; Jung, Birgit; Erb, Klaus J; Peter, Daniel.
Afiliação
  • Bucher H; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Mang S; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Keck M; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Przibilla M; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Lamb DJ; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Schiele F; Immune-Modulation and Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Wittenbrink M; Immune-Modulation and Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Fuchs K; Immune-Modulation and Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Jung B; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Erb KJ; Immune-Modulation and Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany.
  • Peter D; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach an der Riss, Germany. Electronic address: daniel.peter@boehringer-ingelheim.com.
Pulm Pharmacol Ther ; 44: 96-105, 2017 06.
Article em En | MEDLINE | ID: mdl-28315490
ABSTRACT
Smoking is an important risk factor for the development of chronic obstructive pulmonary disease (COPD) and viral infections are believed to be major triggers of exacerbations, which periodically lead to a worsening of symptoms. The pro-inflammatory IL-1 family members IL-1α and IL-1ß are increased in COPD patients and might contribute to disease pathology. We investigated whether individual or combined inhibition of these cytokines reduced lung inflammation in cigarette smoke (CS)-exposed and H1N1-infected BALB/c mice. Animals were treated with individual or combined antibodies (Abs) directed against IL-1α, IL-1ß or IL-1R1. Cells in BAL fluid and cytokines/chemokines in lung homogenate were determined. The viral load was investigated. Blocking IL-1α had significant suppressive effects on total cells, neutrophils, and macrophages. Furthermore, it reduced KC levels significantly. Blocking of IL-1ß did not provide significant activity. In primary human bronchial epithelial air-liquid-interface cell cultures infected with H1N1, IL-1α Abs but not IL-1ß Abs reduced levels of TNF-α and IL-6. Concomitant usage of Abs against IL-1α/IL-1ß revealed strong effects in vivo and reduced total cells, neutrophils and macrophages. Additionally, levels of KC, IL-6, TNF-α, MCP-1, MIP-1α and MIP-1ß were significantly reduced and ICAM-1 and MUC5 A/C mRNA expression was attenuated. The viral load decreased significantly upon combined IL-1α/IL-1ß Ab treatment. Blocking the IL-1R1 provided significant effects on total cells, neutrophils and macrophages but was inferior compared to inhibiting both its soluble ligands IL-1α/IL-1ß. Our results suggest that combined inhibition of IL-1α/IL-1ß might be beneficial to reduce CS/H1N1-induced airway inflammation. Moreover, combined targeting of both IL-1α/IL-1ß might be more efficient compared to individual neutralization IL-1α or IL-1ß or inhibition of the IL-1R1.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 4_TD Base de dados: MEDLINE Assunto principal: Pneumonia / Fumar / Interleucina-1alfa / Interleucina-1beta Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Revista: Pulm Pharmacol Ther Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 4_TD Base de dados: MEDLINE Assunto principal: Pneumonia / Fumar / Interleucina-1alfa / Interleucina-1beta Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Revista: Pulm Pharmacol Ther Ano de publicação: 2017 Tipo de documento: Article