Curcumin is a safe, non‐toxic, readily available and naturally occurring compound, an active constituent of Curcuma longa (turmeric). Curcumin could potentially treat diseases, but faces poor physicochemical and pharmacological characteristics. To overcome these limitations, we developed a stable, water‐soluble formulation of curcumin called cyclodextrin‐complexed curcumin (CDC). We have previously shown that direct delivery of CDC to the lung following lipopolysaccharides exposure reduces acute lung injury (ALI) and effectively reduces lung injury, inflammation and mortality in mice following Klebsiella pneumoniae . Recently, we found that administration of CDC led to a significant reduction in angiotensin‐converting enzyme 2 and signal transducer and activator of transcription 3 expression in gene and protein levels following pneumonia, indicating its potential in treating coronavirus disease 2019 (COVID‐19). In this review, we consider the clinical features of ALI and acute respiratory distress syndrome (ARDS) and the role of curcumin in modulating the pathogenesis of bacterial/viral‐induced ARDS and COVID‐19.

Aspiration‐induced lung injury is a common grievance encountered in the intensive care unit (ICU). It is a significant risk factor for improving ventilator‐associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS). Hypoxia‐inducible factor (HIF)‐1α is one of the primary transcription factors responsible for regulating the cellular response to changes in oxygen tension. Here, we sought to determine the role of HIF‐1α and specifically the role of type 2 alveolar epithelial cells in generating the acute inflammatory response following acid and particles (CASP) aspiration. Previous studies show HIF‐1 α is involved in regulating the hypoxia‐stimulated expression of MCP‐1 in mice and humans. The CASP was induced in C57BL/6, ODD‐Luc, HIF‐1α (+/+) control, and HIF‐1α conditional knockout (HIF‐1α (−/−) mice). Following an injury in ODD mice, explanted organs were subjected to IVIS imaging to measure the degree of hypoxia. HIF‐1α expression, BAL albumin, cytokines, and histology were measured following CASP. In C57BL/6 mice, the level of HIF‐1α was increased at 1 h after CASP. There were significantly increased levels of albumin and cytokines in C57BL/6 and ODD‐Luc mice lungs following CASP. HIF‐1α (+/+) mice given CASP demonstrated a synergistic increase in albumin leakage, increased pro‐inflammatory cytokines, and worse injury. MCP‐1 antibody neutralized HIF‐1α (+/+) mice showed reduced granuloma formation. The NF‐κB expression was increased substantially in the HIF‐1α (+/+) mice following CASP compared to HIF‐1α (−/−) mice. Our data collectively identify that HIF‐1α upregulation of the acute inflammatory response depends on NF‐κB following CASP.

Hypoxia-inducible factors (HIFs) are transcription factors critical for the adaptive response to hypoxia. There is also an essential link between hypoxia and inflammation, and HIFs have been implicated in the dysregulated immune response to various insults. Despite the prevalence of hypoxia in tissue trauma, especially involving the lungs, there remains a dearth of studies investigating the role of HIFs in clinically relevant injury models. Here, we summarize the effects of HIF-1α on the vasculature, metabolism, inflammation, and apoptosis in the lungs and review the role of HIFs in direct lung injuries, including lung contusion, acid aspiration, pneumonia, and COVID-19. We present data that implicates HIF-1α in the context of arguments both in favor and against its role as adaptive or injurious in the propagation of the acute inflammatory response in lung injuries. Finally, we discuss the potential for pharmacological modulation of HIFs as a new class of therapeutics in the modern intensive care unit.

No abstract

No abstract