The role of Duffy antigen receptor for chemokines in acute respiratory distress syndrome

Dysregulated inflammation in response to inciting events leads to severe end-organ dysfunction and failure, contributing to long-term morbidity and, ultimately, potentially death. Duffy antigen receptor for chemokines (DARC), a major regulator of inflammation, plays key roles in a variety of acute and chronic inflammatory states. DARC minimizes the end-organ injury induced in response to an inciting event by acting as a "sink" to soak up excessive inflammatory cytokines and chemokines. Data demonstrate how the lack of DARC functioning is associated with altered immunopathological and clinical responses within a variety of critical illnesses. Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) are the most common and profound of end-organ dysfunctions seen in critically ill and injured patients. ARDS can be induced by either direct causes, such as aspiration or thoracic trauma, or indirectly, such as in response to intraabdominal sepsis. Despite advances in the treatment of critically ill patients, management of ARDS remains focused on a lung-protective low tidal volume strategy. There remains no focused therapy directed at the underlying pathophysiology of ARDS, namely the severely dysfunctional and excessive inflammation from an inciting event. Therapies targeting individual cytokines or pathways have failed to ameliorate the inflammation that is the hallmark of ARDS, and broader-based therapeutic strategies are needed. Therefore, this review focuses on highlighting the importance of DARC as a potential broad-spectrum target for the next generation of therapeutic agents that will be directed toward the inflammatory regulator in ARDS.