rIL-35 prevents murine transfusion-related acute lung injury by inhibiting the activation of endothelial cells.

Abstract

BACKGROUND:

Transfusion-related acute lung injury (TRALI) is an important cause of death associated with transfusion, and no specific clinical treatments are available. Endothelial cells are believed to play an important role in the development of TRALI. This study investigated whether IL-35, an endothelial stabilizing cytokine could regulate the severity of antibody-mediated TRALI in vivo.

STUDY DESIGN AND METHODS:

Human microvascular endothelial cells (HMVECs) were cultured in vitro, rIL-35(2 μg/mL) was added before HMVECs activation, and HMVECs were fully activated by LPS (0.5 μg/mL). Then cells were collected for flow cytometry analysis. We used a previously established "two-event" mouse model of TRALI with naive and lipopolysaccharide (LPS)-injected mice as controls. rIL-35(100 μg/kg) was injected into the tail vein for 3 consecutive days before the induction of the TRALI model. Samples were collected 2 hours after TRALI induction and tested for lung tissue myeloperoxidase activity, total protein levels, lung tissue histology, endothelial cell activation assay, and cytokine assay.

RESULTS:

In vitro culture of HMVECs with rIL-35 verified that rIL-35 inhibited endothelial cells. In a mouse model, prophylactic administration of rIL-35 prevented pulmonary edema, increased lung protein levels, and reduced polymorphonuclear neutrophil accumulation in the lung.

CONCLUSIONS:

This work suggests that antibody-mediated murine TRALI can be prevented by rIL-35, and that rIL-35 appears to work by inhibiting the activation of lung endothelial cells.

• Authors: Jiajia Qiao, Rui He, Yonghua Yin, Li Tian, Ling Li, Zhengqiu Lian, Peng Fang, Zhong Liu
• Journal: Transfusion (Transfusion) Vol. 60 Issue 7 Pg. 1434-1442 (07 2020) ISSN: 1537-2995 [Electronic] United States
• PMID: 32452053 (Publication Type: Journal Article)
• Copyright: © 2020 AABB.

Chemical References

• Interleukins
• Lipopolysaccharides
• Recombinant Proteins
• interleukin-35, mouse

Topics

• Animals
• Disease Models, Animal
• Endothelial Cells (immunology, pathology)
• Humans
• Interleukins (pharmacology)
• Lipopolysaccharides (toxicity)
• Lung (immunology, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Neutrophil Infiltration (drug effects)
• Neutrophils (immunology, pathology)
• Recombinant Proteins (pharmacology)
• Transfusion-Related Acute Lung Injury (chemically induced, drug therapy, immunology, pathology)