TY - JOUR
T1 - Methylprednisolone fails to attenuate lung injury in a mouse model of transfusion related acute lung injury
AU - Müller, Marcella C. A.
AU - Tuinman, Pieter R.
AU - van der Sluijs, Koenraad F.
AU - Boon, Louis
AU - Roelofs, Joris J.
AU - Vroom, Margreeth B.
AU - Juffermans, Nicole P.
PY - 2014
Y1 - 2014
N2 - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Anecdotally, TRALI patients have been treated with corticosteroids. However, evidence for its therapeutic rationale in TRALI is lacking. We determined the effects of corticosteroids on lung injury in a "two-hit" mouse model of antibody-mediated TRALI. BALB/c mice were primed with lipopolysaccharide, after which TRALI was induced by injecting major histocompatibility complex (MHC)-I antibody against H2K(d) . Mice infused with phosphate-buffered saline served as controls. Simultaneously, one group of TRALI mice was infused with methylprednisolone (MPS; 2 mg/kg). Mice were supported by mechanical ventilation for 2 hours, after which bronchoalveolar lavage fluid (BALF) and lung homogenate were obtained. Statistics were obtained by one-way analysis of variance or Kruskal-Wallis. Injection of MHC-I antibodies resulted in TRALI, indicated by pulmonary edema and increased BALF levels of protein and the proinflammatory mediators macrophage inflammatory protein-2, keratinocyte-derived chemokine, and interleukin (IL)-6. Administration of MPS did not affect the amount of edema nor pulmonary protein and chemokine levels. MPS reduced systemic inflammatory reaction as well as IL-6 levels in the BALF. In a two-hit model of antibody-mediated TRALI, MPS attenuated the IL-6 host response, but failed to prevent the development of lung injury
AB - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Anecdotally, TRALI patients have been treated with corticosteroids. However, evidence for its therapeutic rationale in TRALI is lacking. We determined the effects of corticosteroids on lung injury in a "two-hit" mouse model of antibody-mediated TRALI. BALB/c mice were primed with lipopolysaccharide, after which TRALI was induced by injecting major histocompatibility complex (MHC)-I antibody against H2K(d) . Mice infused with phosphate-buffered saline served as controls. Simultaneously, one group of TRALI mice was infused with methylprednisolone (MPS; 2 mg/kg). Mice were supported by mechanical ventilation for 2 hours, after which bronchoalveolar lavage fluid (BALF) and lung homogenate were obtained. Statistics were obtained by one-way analysis of variance or Kruskal-Wallis. Injection of MHC-I antibodies resulted in TRALI, indicated by pulmonary edema and increased BALF levels of protein and the proinflammatory mediators macrophage inflammatory protein-2, keratinocyte-derived chemokine, and interleukin (IL)-6. Administration of MPS did not affect the amount of edema nor pulmonary protein and chemokine levels. MPS reduced systemic inflammatory reaction as well as IL-6 levels in the BALF. In a two-hit model of antibody-mediated TRALI, MPS attenuated the IL-6 host response, but failed to prevent the development of lung injury
U2 - https://doi.org/10.1111/trf.12394
DO - https://doi.org/10.1111/trf.12394
M3 - Article
C2 - 24032748
SN - 0041-1132
VL - 54
SP - 996
EP - 1001
JO - Transfusion
JF - Transfusion
IS - 4
ER -