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C1 inhibitor attenuates pulmonary inflammation in an in vivo model of transfusion-related acute lung injury

Introduction

Transfusion-related acute lung injury (TRALI) has a high incidence in critically ill and surgical patients and contributes to adverse outcome, while specific therapy is absent. Recently it was demonstrated that complement activation plays a pivotal role in TRALI. We aimed to determine whether a C1 inhibitor is beneficial in a two-hit mouse model of antibody-mediated TRALI.

Methods

BALB/c mice were primed with lipopolysaccharide (LPS, from E. coli 0111:B4) that was administered intraperitoneally in a dose of 0.1 mg/kg, after which TRALI was induced by injecting MHC-I antibody against H2Kd (IgG2a,k) at a dose of 2 mg/kg. Mice infused with PBS or LPS served as controls. Concomitantly, mice infused with the MHC-I antibody were treated with C1 inhibitor (Cetor®; Sanquin, Amsterdam, the Netherlands) in a dose of 400 IU/kg intravenously. After infusion, mice were mechanically ventilated with a lung-protective pressure-controlled mode for 2 hours and then sacrificed, after which a bronchoalveolar lavage (BAL) was done. Statistics were analyzed by one-way ANOVA, values expressed as mean and standard deviation.

Results

Injection of LPS and MHC-I antibodies resulted in TRALI, indicated by increased levels of protein in the BAL fluid, wet/dry ratios and levels of KC, MIP-2 and IL-6. C1 inhibitor Cetor® significantly reduced total protein in BAL fluid from 792 (169) to 421 (230) μg/ml (P < 0.001) and tended to reduce the wet/dry ratio from 5.3 ± 0.3 to 4.9 ± 0.5 (P = 0.09). Cetor® also reduced BALF levels of MIP-2 from 214 (54) to 127 (22) pg/ml (P < 0.01). KC and IL-6 levels were not affected.

Conclusion

In a model of antibody-mediated TRALI, C1 inhibitor attenuated pulmonary inflammation. C1 inhibition may be a potential beneficial intervention in TRALI.

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Correspondence to M Müller.

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Müller, M., Tuinman, P., Jongsma, G. et al. C1 inhibitor attenuates pulmonary inflammation in an in vivo model of transfusion-related acute lung injury. Crit Care 17, P372 (2013). https://doi.org/10.1186/cc12310

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Keywords

  • Mouse Model
  • Total Protein
  • Emergency Medicine
  • Pivotal Role
  • Adverse Outcome