Rationale: The incidence and prevalence of allergic asthma, caused by Th2 mediated inflammation in response to environmental antigens, is increasing. Epidemiological 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 towards 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, while controls were sham-sensitized with adjuvant only. After 4 weeks, MALP-2 and IFN- or NaCl, respectively, were intratracheally instillated. After inhalative 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 (BALF) and lungs. Results: Sensitized, NaCl-treated mice developed marked AHR compared to sham-sensitized animals. This coincided with eosinophilia as well as the amplification of eotaxin and the Th2 cytokines IL-5 and IL-13 in the BALF. Treatment of sensitized mice with MALP-2 and IFN- significantly reduced AHR compared to 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.