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  • Invited speaker presentation
  • Open Access

Immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome

  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2 and
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Malaria Journal20109 (Suppl 2) :I13

https://doi.org/10.1186/1475-2875-9-S2-I13

  • Published:

Keywords

  • Dexamethasone
  • Malaria
  • Plasmodium
  • Pulmonary Edema
  • Malaria Infection
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.
Figure 1
Figure 1

Histopathology of P. berghei NK65-induced MA-ARDS. Frozen sections of lungs of mice infected for 10 days with P. berghei NK65 or control mice were stained with H&E.The black bar corresponds with 100 μm.

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.

Authors’ Affiliations

(1)
Laboratory of Immunobiology, Rega Institute, University of Leuven, Belgium
(2)
Laboratory of Molecular Immunoloby, Rega Institute, University of Leuven, Belgium

References

  1. 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.View ArticlePubMedGoogle Scholar

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