The Congressionally Directed Medical Research Program (CDMRP) and the Peer Reviewed Medical Research Program Investigator-Initiated Research Award of the Department of Defense has funded Neil Aggarwal, assistant professor in the Division of Pulmonary, and partnering PI Nicola Heller with $1.5 million over 3 years to conduct research relating to Acute Respiratory Distress Syndrome (ARDS).
ARDS is a devastating illness with an annual U.S. mortality of 60,000-80,000. ARDS often occurs as a by-product of the body’s response to local or systemic inflammatory insults. The resulting damage prevents the lungs from transferring sufficient oxygen to their bloodstream and to vital organs. Currently, there are no treatments for ARDS. Therefore, strategies to harness the power of the immune system to accelerate lung repair processes may have a powerful impact.
Neil and colleagues have found that a protein factor, interleukin-4 or IL-4, can heal and repair lungs damaged in experimental ARDS models. Activation of lung macrophages is central to the beneficial effects of IL-4 treatment. Because a significant percentage of lung macrophages come from monocytes recruited from the bloodstream, the hypothesis is that activation of these blood monocytes by IL-4 is vital to accelerate repair from ARDS-induced damage. They plan to test the efficacy of IL-4-activated monocytes in experimental ARDS models, and use nanoparticle-sized delivery devices called backpacks that can keep IL-4 adherent to the monocytes and enhance their reparative, healing capacity.
In patients with ARDS, it is not known whether blood monocytes are also the primary source of reparative macrophages. The investigators will activate blood monocytes from ARDS patients with IL-4 to convert them to a wound-healing sub-type, with the goal to re-infuse them into patients with ARDS. However, they first need to determine whether IL-4 exposure to monocytes from ARDS patients can generate a wound-healing macrophage by comparing them to IL-4-exposed monocytes from healthy individuals.