Premium
Antibodies to TNF‐α Soluble Receptors Exacerbate Airway Inflammation in a Mouse Model of Asthma
Author(s) -
Kim Jiyoun,
Vaickus Louis,
Bouchard Jacqueline,
Schuller Elizabeth,
Remick Daniel G
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.31.6
Subject(s) - bronchoalveolar lavage , tumor necrosis factor alpha , immunology , medicine , inflammation , asthma , chemokine , antibody , receptor , lung
We investigated TNF soluble receptor (TNF‐SR) regulation of airway TNF‐α expression to determine mediators responsible for exacerbation of pulmonary inflammation and airway hyperresponsiveness (AHR). A house dust extract (HDE) containing cockroach allergens and endotoxin was used to immunize BALB/c mice on day 0 with 2 additional pulmonary challenges on d14 and d21. Groups of mice received a mixture of rat anti TNF‐α SR I and II antibodies (Abs), or rat IgG. Two hrs after the last HDE challenge AHR was measured and bronchoalveolar lavage (BAL) fluid collected. Abs to TNF‐α SR essentially depleted pulmonary TNF‐α SR I and II while the airway concentration of TNF‐α was significantly increased compared to control Abs. Total inflammatory cells were reduced, primarily due to fewer neutrophils despite increases in the CXC chemokines KC and MIP‐2. Blockade of TNF‐SRs increased AHR.IgG Anti TNF SR Abs P valueTNF‐α (pg/ml) 5371 ±641 14498 ± 2988 0.007 TNF‐sRI 143 ±9 16 ± 2 < 0.0001 TNF‐sRII 2829 ±204 7 ± 1 <0.0001 Total cells (x1000) 657 ± 215 960 ± 334 0.049 Neutrophils (x1000) 557 ± 200 868 ± 331 0.039 KC (pg/ml) 1227 ±415 1997±247 0.021 MIP‐2 (pg/ml) 2081 ±647 3704±670 0.023 AHR (% increase of Penh) 180±21 285±45 0.04These results demonstrate that blocking both TNF‐α SR I and II significantly increases AHR and exacerbates the asthma‐like pulmonary inflammation via increased expression of TNF and CXC chemokines in a mouse model of asthma. This work was supported by NIH Grant R01 ES0135283‐03.