Immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome
Malaria Journal volume 9, Article number: I13 (2010)
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. To develop a new animal model for MA-ARDS, mice were infected with Plasmodium berghei NK65, and the development of MA-ARDS was characterized by increased lung weight, edema, leukocyte infiltration and hemorrhages (Figure 1). The pulmonary expression of several cytokines and chemokines was increased to a higher level than in mice infected with P. 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.
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.
Van den Steen PE, Geurts N, Deroost K, Van Aelst I, Verhenne S, Heremans H, Van Damme J, Opdenakker G: Immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome. Am J Respir Crit Care Med. 2010, 181: 957-68. 10.1164/rccm.200905-0786OC.
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Van den Steen, P.E., Geurts, N., Deroost, K. et al. Immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome. Malar J 9 (Suppl 2), I13 (2010). https://doi.org/10.1186/1475-2875-9-S2-I13