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 Associated Receptor for Chemokines (DARC), a major regulator of inflammation, play key roles in a variety of acute and chronic inflammatory states. DARC acts to minimize the end-organ injury induced in response to an inciting event, by acting as a "sink" to soak up excessive inflammatory cytokines and chemokines. Increasing data is available demonstrating 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) or Acute Lung Injury(ALI) is the most common and profound of end-organ dysfunction 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 management 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 it the hallmark of ARDS and future therapeutic strategies will need to be broader based. Therefore, this review will focus on highlighting the importance of DARC as a potential broad spectrum target for the next generation of therapeutic agents that will be directed towards inflammatory regulator in ARDS.
Moscinski et al. (2026) studied this question.