Linked Life Data

9862743

Source:http://linkedlifedata.com/resource/pubmed/id/9862743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-1-22
pubmed:abstractText
We have used a mouse model of allergen-induced airway hyperresponsiveness to demonstrate that immunostimulatory DNA sequences (ISS) containing a CpG DNA motif significantly inhibit airway eosinophilia and reduce responsiveness to inhaled methacholine. ISS not only inhibited eosinophilia of the airway (by 93%) and lung parenchyma (91%), but also significantly inhibited blood eosinophilia (86%), suggesting that ISS was exerting a significant effect on the bone marrow production of eosinophils. The inhibition of the bone marrow production of eosinophils by 58% was associated with a significant inhibition of T cell-derived cytokine generation (IL-5, granulocyte-macrophage CSF, and IL-3). ISS exerted this inhibitory effect on T cell cytokine production indirectly by stimulating monocytes/macrophages and NK cells to generate IL-12 and IFNs. The onset of the ISS effect on reducing the number of tissue eosinophils was both immediate (within 1 day of administration) and sustained (lasted 6 days), and was not due to ISS directly inducing eosinophil apoptosis. ISS was effective in inhibiting eosinophilic airway inflammation when administered either systemically (i.p.), or mucosally (i.e., intranasally or intratracheally). Interestingly, a single dose of ISS inhibited airway eosinophilia as effectively as daily injections of corticosteroids for 7 days. Moreover, while both ISS and corticosteroids inhibited IL-5 generation, only ISS was able to induce allergen-specific IFN-gamma production and redirect the immune system toward a Th1 response. Thus, systemic or mucosal administration of ISS before allergen exposure could provide a novel form of active immunotherapy in allergic diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7054-62
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9862743-Adjuvants, Immunologic, pubmed-meshheading:9862743-Administration, Intranasal, pubmed-meshheading:9862743-Allergens, pubmed-meshheading:9862743-Animals, pubmed-meshheading:9862743-Anti-Inflammatory Agents, pubmed-meshheading:9862743-Bone Marrow, pubmed-meshheading:9862743-Bronchial Hyperreactivity, pubmed-meshheading:9862743-Bronchial Provocation Tests, pubmed-meshheading:9862743-CpG Islands, pubmed-meshheading:9862743-Desensitization, Immunologic, pubmed-meshheading:9862743-Dexamethasone, pubmed-meshheading:9862743-Disease Models, Animal, pubmed-meshheading:9862743-Drug Evaluation, Preclinical, pubmed-meshheading:9862743-Eosinophils, pubmed-meshheading:9862743-Female, pubmed-meshheading:9862743-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:9862743-Hypereosinophilic Syndrome, pubmed-meshheading:9862743-Interferon-gamma, pubmed-meshheading:9862743-Interleukin-3, pubmed-meshheading:9862743-Interleukin-5, pubmed-meshheading:9862743-Methacholine Chloride, pubmed-meshheading:9862743-Mice, pubmed-meshheading:9862743-Mice, Inbred BALB C, pubmed-meshheading:9862743-Oligodeoxyribonucleotides, pubmed-meshheading:9862743-Ovalbumin, pubmed-meshheading:9862743-Plethysmography, Whole Body, pubmed-meshheading:9862743-Pulmonary Eosinophilia, pubmed-meshheading:9862743-Th2 Cells, pubmed-meshheading:9862743-Trachea
pubmed:year
1998
pubmed:articleTitle
Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice.
pubmed:affiliation
Department of Medicine, University of California at San Diego, La Jolla 92093-0635, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't