DOI: 10.4049/jimmunol.161.12.7054. Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice

Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice

10.4049/jimmunol.161.12.7054

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

AbstractWe 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-γ 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.

Bibliography

Broide, D., Schwarze, J., Tighe, H., Gifford, T., Nguyen, M.-D., Malek, S., Van Uden, J., Martin-Orozco, E., Gelfand, E. W., & Raz, E. (1998). Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice. The Journal of Immunology, 161(12), 7054â7062.

Authors 10

David Broide (first)
Jurgan Schwarze (additional)
Helen Tighe (additional)
Tim Gifford (additional)
Minh-Duc Nguyen (additional)
Siamak Malek (additional)
John Van Uden (additional)
Elena Martin-Orozco (additional)
Erwin W. Gelfand (additional)
Eyal Raz (additional)

References 30 Referenced 307

Dates

Type	When
Created	2 years, 7 months ago (Dec. 30, 2022, 12:43 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 1:32 p.m.)
Indexed	3 weeks, 6 days ago (Aug. 2, 2025, 1:05 a.m.)
Issued	26 years, 8 months ago (Dec. 15, 1998)
Published	26 years, 8 months ago (Dec. 15, 1998)
Published Print	26 years, 8 months ago (Dec. 15, 1998)

Funders 0

None

BibTeX

@article{Broide_1998, title={Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice}, volume={161}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.161.12.7054}, DOI={10.4049/jimmunol.161.12.7054}, number={12}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Broide, David and Schwarze, Jurgan and Tighe, Helen and Gifford, Tim and Nguyen, Minh-Duc and Malek, Siamak and Van Uden, John and Martin-Orozco, Elena and Gelfand, Erwin W. and Raz, Eyal}, year={1998}, month=dec, pages={7054–7062} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>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-\u03b3 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.</jats:p>",
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