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Title: Immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome
Authors: Van den Steen, Philippe ×
Geurts, Nathalie
Deroost, Katrien
Van Aelst, Ilse
Verhenne, Sebastien
Heremans, Hubertine
Van Damme, Jozef
Opdenakker, Ghislain #
Issue Date: May-2010
Publisher: American Lung Association
Series Title: American Journal of Respiratory and Critical Care Medicine vol:181 issue:9 pages:957-968
Abstract: RATIONALE: Malaria infection is often complicated by malaria-associated acute respiratory distress syndrome (MA-ARDS), characterized by pulmonary edema and hemorrhages. No efficient treatments are available for MA-ARDS and its pathogenesis remains poorly understood. OBJECTIVES: Development of a new animal model for MA-ARDS to explore the pathogenesis and possible treatments. METHODS: C57BL/6 mice were infected with Plasmodium berghei NK65, and the development of MA-ARDS was evaluated by the analysis of lung weight, histopathology, and bronchoalveolar lavages. Cytokine and chemokine expression in the lungs was analyzed by reverse transcription-polymerase chain reaction, and the accumulation of leukocyte subclasses was determined by flow cytometric analysis. MEASUREMENTS AND MAIN RESULTS: In this model, the pulmonary expression of several cytokines and chemokines was increased to a higher level than in mice infected with Plasmodium chabaudi AS, which does not cause MA-ARDS. By depletion experiments, CD8(+) T lymphocytes were shown to be pathogenic. High doses of dexamethasone blocked MA-ARDS, even when administered after appearance of the complication, and reduced pulmonary leukocyte accumulation and the expression of a monocyte/macrophage-attracting chemokine. CONCLUSIONS: We developed a novel model of MA-ARDS with many similarities to human MA-ARDS and without cerebral complications. This contrasts with the more classical model with P. berghei ANKA, characterized by fulminant cerebral malaria. Hence, infection with P. berghei NK65 generates a broader time window to study the pathogenesis and to evaluate candidate treatments. The finding that high doses of dexamethasone cured MA-ARDS suggests that it might be more effective against MA-ARDS than it was in the clinical trials for cerebral malaria.
URI: 
ISSN: 1073-449X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
Faculty of Science, Campus Kulak Kortrijk
Laboratory of Molecular Immunology (Rega Institute)
× corresponding author
# (joint) last author

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