Efficacy of macrophage-activating lipopeptide-2 combined with interferon-gamma in a murine asthma model.

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.

• Authors: Henning Weigt, Christina Nassenstein, Thomas Tschernig, Peter F Mühlradt, Norbert Krug, Armin Braun
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 172 Issue 5 Pg. 566-72 (Sep 01 2005) ISSN: 1073-449X [Print] United States
• PMID: 15901606 (Publication Type: Journal Article)

Chemical References

• Immunologic Factors
• Lipopeptides
• Oligopeptides
• Interferon-gamma
• macrophage stimulatory lipopeptide 2

Topics

• Administration, Inhalation
• Animals
• Asthma (complications, drug therapy, immunology)
• Bronchial Hyperreactivity (drug therapy, immunology)
• Disease Models, Animal
• Immunologic Factors (administration & dosage)
• Interferon-gamma (administration & dosage)
• Lipopeptides
• Macrophage Activation (drug effects, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Oligopeptides (administration & dosage)
• Th2 Cells (immunology)