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


CONCLUSIONS
These data demonstrate the in vivo efficacy of MALP-2 and IFN-gamma to reduce allergic inflammation and AHR in allergic asthma.
Weigt
Henning
H
Department of Immunology, Allergology, and Clinical Inhalation, Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany. braun@item.fraunhofer.de
Nassenstein
Christina
C
Tschernig
Thomas
T
Mühlradt
Peter F
PF
Krug
Norbert
N
Braun
Armin
A
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage*; D055666:Lipopeptides; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage*; D018418:Th2 Cells / Q000276:immunology
D007155:Immunologic Factors; D055666:Lipopeptides; D009842:Oligopeptides; D007371:Interferon-gamma; C106335:macrophage stimulatory lipopeptide 2