Study examines role of NLRP3 inflammasome in ventilator-induced lung injury

Mechanical ventilation is often lifesaving, but can also initiate or aggravate lung injury. A new study in the May issue of Anesthesiology examined the role of one particular receptor in the inflammatory pathway, the NLRP3 inflammasome, and whether it impacts ventilator-induced lung injury.

The NLRP3 inflammasome is an important receptor of the innate immune system which is activated by danger-signaling molecules released from injured tissue. During mechanical ventilation, lung cells can be injured and release danger-signaling molecules which initiate an inflammatory response that can produce further tissue damage.

"Since mechanical ventilation is often used during general anesthesia and in the treatment of patients with acute respiratory failure, it is important to understand the negative side effects it can have," said lead study author Maria Kuipers, M.D., Laboratory of Experimental Intensive Care and Anesthesiology of the Academic Medical Center, University of Amsterdam. "In particular, one serious risk is development of ventilator-induced lung injury. The resulting inflammatory state can make the lung more susceptible to other pathologies."

Since the exact pathways involved in the immune system's response to mechanical ventilation are unknown, researchers closely examined the role of the NLRP3 inflammasome. The up-regulation of the NLRP3 gene was analyzed in respiratory epithelial cells and alveolar macrophages obtained from ventilated patients. In addition, mice were treated with mechanical ventilation to further understand the role of the NLRP3 inflammasome in lung injury.

Findings showed that in patients ventilated for five hours during elective surgery, NLRP3 levels in alveolar macrophages were increased. The study also found NLRP3 inflammasome-deficient mice displayed less ventilator-induced lung injury from mechanical ventilation compared with normal mice.

"Another major finding from our study was that treatment with interleukin-1 receptor antagonist or glibenclamide also reduced ventilator-induced lung injury," said Dr. Kuipers. "We believe these results can help improve future treatment possibilities in which the NLRP3 inflammasome may serve as a potential therapeutic target."

Most patients who receive general anesthesia do not have lung injury. However, obese patients and others undergoing long duration surgeries are more susceptible to lung injury during mechanical ventilation. Future research is needed to examine the role of innate immunity in the regulation of ventilator-induced lung injury. Related research could help anesthesiologists minimize ventilator-induced lung injury in patients undergoing general anesthesia.

Source: Anesthesiology