Inhaled aerosolized insulin: a "topical" anti-inflammatory treatment for acute lung injury and respiratory distress syndrome?

Abstract

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are forms of pulmonary edema that result from robust local and systemic inflammatory states, such as sepsis. The morbidity and mortality associated with ALI and ARDS are significant and the treatment of these conditions presents a formidable challenge. Controlling hyperglycemia with insulin is a core component of patient management in the critically ill. Insulin treatment also exerts beneficial metabolic effects beyond glucose control, as well as non-metabolic effects, in insulin-resistant states. For instance, insulin inhibits NF-kappaB--dependent synthesis of pro-inflammatory factors and attenuates production of ROS. Indeed, intravenous administration of insulin ameliorates pulmonary injury and dysfunction in the LPS model of ALI. Most recently, an inhalable insulin formulation was shown to effectively reduce glucose concentrations with minimal impact on long-term pulmonary function. We propose that administering inhalable insulin to hyperglycemic ALI/ARDS patients could directly reduce alveolar inflammation while reducing circulating glucose levels.