Research in Brief: Immune Cells May Reduce Lung Injury

Study Mimicking Life-Threatening Inflammation Common in ICU Patients Shows Potential Protective Role of Immune Cells

Acute respiratory distress syndrome (ARDS) drew wide attention during the COVID-19 pandemic as a leading cause of death in patients with severe cases. Now, a new preclinical study from Beth Israel Deaconess Medical Center (BIDMC) and Massachusetts General Hospital (MGH) reveals a novel approach to mitigating lung damage caused by prolonged exposure to high oxygen levels—a condition that mimics key features of ARDS, including widespread inflammation and damage to the lungs.

In findings published in Anesthesia and Analgesia, the investigators demonstrated that a single administration of B cells decreased the severity of lung injury, improved oxygenation and promoted a more balanced immune response (improved immune function without the risk of runaway inflammation) in a small animal model of ARDS. B cells are type of white blood cell that play a central role in the immune system by producing antibodies, but they also help regulate immune responses by coordinating with other cells of the immune system and calming excessive inflammation.

“ARDS develops in at least one in ten mechanically ventilated patients in the intensive care unit, and has a high mortality rate,” said lead author Dusan Hanidziar, MD, PhD, a postdoctoral research fellow in the Center for Inflammation Research at BIDMC and an instructor in Anesthesia at MGH and Harvard Medical School. “New, targeted treatments need to be developed for clinical use, and we’re excited that our data suggest harnessing the functions of the B cell may represent a novel therapy for ARDS.”

In this first-of-its-kind study, Hanidziar and colleagues showed that, in mice exposed to high oxygen levels, the number of B cells dropped sharply in both the lungs and the bloodstream. Administering B cells intravenously 24 hours after the onset of high oxygen exposure, improved immune regulation, reduced harmful inflammation, and partially restored the diversity of immune cells in the animals’ lungs.

“We’ve known that high oxygen levels can severely disrupt immune balance in the lungs, but this study shows that infusing B cells can help correct that imbalance and reduce lung injury,” said senior author Simon C Robson, MD, PhD, director of the Center for Inflammation Research. “This work lays important groundwork for exploring B-cell therapy as a potential treatment for ARDS and related conditions.”

BILH co-authors included: Eva Csizmadia, MS; Juan D. Valencia, MD, MPH; and Leo E. Otterbein, PhD. MGH co-authors were Ruxandra Sirbulescu, PhD and Mark C. Poznansky, MD, PhD from MGH Vaccine and Immunotherapy Center (VIC).

Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Numbers K08HL141694, R03HL171347, and from National Institute of Neurological Disorders and Stroke under award number R01NS117598. Philanthropic support was provided by Jeff and Judy Buzen, and donations to Vaccine and Immunotherapy Center Innovation Fund.