Oxygen, Inflammation & Hypoxia-Inducible Factor (HIF-1)

Scientists in Germany have shown that microenvironment of inflamed and injured tissues are typically characterized by low levels of oxygen and glucose and high levels of inflammatory cytokines, reactive oxygen, and nitrogen species and metabolites. Recent medical research has suggested that there is a strong link between cell hypoxia (oxygen deficiency in cells) and chronic inflammatory processes.

Inflammation is the most common causes of tissue hypoxia and/or decreased circulation. Both inflamed tissues as well as the areas surrounding malignant tumors are characterized by hypoxia and low concentrations of glucose. Inflammation can lead to sepsis, circulatory collapse and ultimately multi-system organ failure.

Tissue hypoxia is manifested in increased levels of hypoxia-inducible factor (HIF-1) (this factor and cell hypoxia are key factors in the progress of cancer). Elevated HIF-1 triggers a cascade of events with involvement of pro-inflammatory transcription factors such as nuclear factor kappa B (or NF-kappaB) and activator protein AP-1.

Hypoxia-inducible factor 1 (HIF-1) is known to be a master regulator of hypoxic response. Researchers have found that low levels of magnesium suppresses reactive-oxygen-species- (ROS) induced HIF-1. HIF-1a regulates the expression of at least 30 genes when oxygen levels are low. Magnesium deficiency depresses HIF-1 activity. This is the basis of excessive inflammatory immune response (sepsis) that contributes to the patient’s death. On intensive care units, sepsis is the second-most common cause of death worldwide.