Efficacy of macrophage-activating lipopeptide-2 combined with interferon-gamma in a murine asthma model.
Am J Respir Crit Care Med
; 172(5): 566-72, 2005 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-15901606
ABSTRACT
RATIONALE The incidence and prevalence of allergic asthma, caused by Th2-mediated inflammation in response to environmental antigens, is increasing. Epidemiologic data suggest that a lack of Th1-inducing factors may play a pivotal role in the development of this disease. We have previously shown that dendritic cells treated with macrophage-activating lipopeptide-2 (MALP-2) combined with IFN-gamma modulate the Th2 response toward Th1 in an in vitro allergy model. OBJECTIVE:
To test in vivo efficacy of this regime, the effects of the substances were evaluated in a mouse model of allergic airway inflammation.METHODS:
Female Balb/c mice were sensitized to ovalbumin, whereas control animals were sham-sensitized with adjuvant only. After 4 weeks, MALP-2 and IFN-gamma or NaCl, respectively, were intratracheally instillated. After inhalational ovalbumin challenge, airway hyperreactivity (AHR) to inhaled methacholine was measured by head-out body plethysmography. The animals were subsequently killed to sample bronchoalveolar lavage fluid and lungs.RESULTS:
Sensitized NaCl-treated mice developed marked AHR compared with sham-sensitized animals. This coincided with eosinophilia as well as the amplification of eotaxin and the Th2 cytokines interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluid. Treatment of sensitized mice with MALP-2 and IFN-gamma significantly reduced AHR compared with the sensitized, NaCl-treated positive control. Eosinophilia as well as Th2 cytokines were reduced to the levels of unsensitized animals. In contrast, IL-12p70 and neutrophils were markedly increased by treatment with both substances.CONCLUSION:
These data demonstrate the in vivo efficacy of MALP-2 and IFN-gamma to reduce allergic inflammation and AHR in allergic asthma.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Asthma
/
Interferon-gamma
/
Bronchial Hyperreactivity
/
Immunologic Factors
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Am J Respir Crit Care Med
Journal subject:
TERAPIA INTENSIVA
Year:
2005
Document type:
Article
Affiliation country:
Germany
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA