Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides

Sanjiv Sur, James S. Wild, Barun Choudhury, Nilanjana Sur, Rafeul Alam, Dennis M. Klinman

Research output: Contribution to journalArticle

354 Citations (Scopus)

Abstract

Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-γ to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-γ -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-γ in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma.

Original languageEnglish (US)
Pages (from-to)6284-6293
Number of pages10
JournalJournal of Immunology
Volume162
Issue number10
StatePublished - May 15 1999

Fingerprint

Oligodeoxyribonucleotides
Pneumonia
Asthma
Allergens
Ambrosia
Cytokines
Eosinophils
Aptitude
Interleukin-4
Immunoglobulin E
Morbidity
Mortality
Incidence
Inhibition (Psychology)

ASJC Scopus subject areas

  • Immunology

Cite this

Sur, S., Wild, J. S., Choudhury, B., Sur, N., Alam, R., & Klinman, D. M. (1999). Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. Journal of Immunology, 162(10), 6284-6293.

Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. / Sur, Sanjiv; Wild, James S.; Choudhury, Barun; Sur, Nilanjana; Alam, Rafeul; Klinman, Dennis M.

In: Journal of Immunology, Vol. 162, No. 10, 15.05.1999, p. 6284-6293.

Research output: Contribution to journalArticle

Sur, S, Wild, JS, Choudhury, B, Sur, N, Alam, R & Klinman, DM 1999, 'Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides', Journal of Immunology, vol. 162, no. 10, pp. 6284-6293.
Sur S, Wild JS, Choudhury B, Sur N, Alam R, Klinman DM. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. Journal of Immunology. 1999 May 15;162(10):6284-6293.
Sur, Sanjiv ; Wild, James S. ; Choudhury, Barun ; Sur, Nilanjana ; Alam, Rafeul ; Klinman, Dennis M. / Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. In: Journal of Immunology. 1999 ; Vol. 162, No. 10. pp. 6284-6293.
@article{e16dea61b5854e76ac75a8f5d8c60ddc,
title = "Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides",
abstract = "Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-γ to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-γ -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-γ in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma.",
author = "Sanjiv Sur and Wild, {James S.} and Barun Choudhury and Nilanjana Sur and Rafeul Alam and Klinman, {Dennis M.}",
year = "1999",
month = "5",
day = "15",
language = "English (US)",
volume = "162",
pages = "6284--6293",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides

AU - Sur, Sanjiv

AU - Wild, James S.

AU - Choudhury, Barun

AU - Sur, Nilanjana

AU - Alam, Rafeul

AU - Klinman, Dennis M.

PY - 1999/5/15

Y1 - 1999/5/15

N2 - Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-γ to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-γ -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-γ in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma.

AB - Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-γ to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-γ -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-γ in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma.

UR - http://www.scopus.com/inward/record.url?scp=0033563211&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033563211&partnerID=8YFLogxK

M3 - Article

VL - 162

SP - 6284

EP - 6293

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -