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Efficacy of Macrophage-activating Lipopeptide-2 Combined with Interferon- in a Murine Asthma Model

Department of Immunology, Allergology, and Clinical Inhalation, Fraunhofer Institute of Toxicology and Experimental Medicine; Functional and Applied Anatomy, Medical School of Hannover, Hannover; and Wound Healing Research Group, BioTec Gruenderzentrum, Braunschweig, Germany

Correspondence and requests for reprints should be addressed to Dr. Armin Braun, Head of Immunology and Allergology, Fraunhofer ITEM, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany. E-mail: braun{at}item.fraunhofer.de

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- 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- 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- 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- to reduce allergic inflammation and AHR in allergic asthma.

Key Words: immunotherapy • mouse • Th1/Th2 cells • Toll-like receptor

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