Immune cell metabolism may point to PAH treatment strategy
Study links metabolism changes to inflammatory cytokines
A study found that changes in immune cell metabolism may underlie increases in inflammatory signaling molecules in people with pulmonary arterial hypertension (PAH), suggesting that targeting immune cell metabolism could be a treatment strategy for the condition.
The study, “Metabolic changes of peripheral blood mononuclear cells are related to the high cytokine levels in patients with pulmonary arterial hypertension,” was published in Life Sciences.
Inflammation is a protective mechanism employed by the immune system to fight off infection. But uncontrolled inflammation may cause or worsen health problems. Studies have suggested that uncontrolled inflammation may play a role in PAH, a disorder marked by high pressure in the vessels that carry blood through the lungs. People with PAH tend to have increased levels of pro-inflammatory cytokines (immune signaling molecules). However, the mechanisms underlying increased cytokine levels and inflammation in PAH are not fully understood.
Researchers in Mexico collected blood samples from 20 people with PAH and eight people without the disease. They used the blood samples to isolate immune cells and measure the levels of several cytokines. They then conducted a battery of statistical analyses to look for correlations between changes in immune cell metabolism — that is, how immune cells are using energy — and cytokine levels.
They found that people with PAH had higher levels of HIF-1 alpha and AMPK, two proteins that act as master regulators of cellular metabolism. Levels of several proteins involved in energy production, including some of the so-called OXPHOS complexes, also were higher in immune cells from people with PAH.
Metabolic changes and cytokine levels
The researchers found that there were statistically significant associations between the metabolic changes and alterations in inflammatory cytokines. For example, higher levels of HIF-1 alpha were associated with higher levels of IL-1 beta, IL-8, and IL-17 A, all of which are pro-inflammatory cytokines that had been found to be elevated in people with PAH.
“These results suggest that the metabolic changes detected at the protein level could predict the levels of cytokines in the peripheral circulation of patients with PAH,” the researchers wrote.
The researchers speculated that immune cells in PAH may undergo metabolic changes because the disease causes problems with the body’s ability to absorb oxygen that’s normally needed for cells to generate energy. This, in turn, could lead immune cells to produce and release more cytokines, driving inflammation in PAH.
If that’s true, it may be possible to treat PAH by normalizing immune cell metabolism to reduce inflammation. The researchers stressed, however, that their study was based on a small number of patients, so further studies will be needed to validate the findings and elucidate the underlying mechanisms in more detail.
About the Author
