New treatment for sepsis and lupus could be on the horizon

DUBLIN, Ireland — A recent scientific discovery could lead to a new treatment for sepsis. This breakthrough could also potentially benefit the treatment of various other conditions, from COVID-19 to autoimmune diseases such as arthritis and lupus.

Researchers found that an enzyme known as Fumarate Hydratase (FH), found within white blood cells called macrophages, becomes suppressed during immune responses. Macrophages can often overreact when combating invasive pathogens.

“No one has made a link from Fumarate Hydratase to inflammatory macrophages before,” says lead author Professor Luke O’Neill from Trinity College Dublin, in a media release. “And we feel that this process might be targetable to treat debilitating diseases like lupus, which is a nasty autoimmune disease that damages several parts of the body including the skin, kidneys, and joints.”

The role of FH is crucial as it prevents messenger molecules from the cell’s power stations (mitochondria) from triggering a “cytokine storm” — an intense immune reaction that can result in fatalities from sepsis and COVID-19.

“We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases,” says joint first author Christian Peace, a Ph.D. student in Professor O’Neill’s lab. “We found that when Fumarate Hydratase is repressed, RNA is released from mitochondria which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This process could potentially be targeted therapeutically.”

Inflammation spelled out with stethoscope
(© tutul_1410 –

This study offers new insights into the mechanisms at work during the progression of inflammatory diseases. In a mouse model of lupus, researchers found that Fumarate Hydratase was suppressed, a condition that often arises during bacterial and viral infections and can prove fatal. Additionally, patient blood samples revealed a significant reduction in the presence of the protein.

“Restoring Fumarate Hydratase in these diseases or targeting MDA5 or TLR7, therefore, presents an exciting prospect for badly needed new anti-inflammatory therapies,” suggests Prof. O’Neill.

In a related study conducted by another Trinity team, similar findings regarding kidney cancer were made.

“Because the system can go wrong in certain types of cancer, the scope of any potential therapeutic target could be widened beyond inflammation,” adds O’Neill.

Sepsis has a mortality rate as high as 50 percent in people with septic shock. These patients require intensive care to support their organs while the infection is being treated.

The study is published in the journal Nature.

What is lupus?

Lupus, or systemic lupus erythematosus (SLE), is a chronic autoimmune disease. In this disease, the body’s immune system mistakenly attacks healthy tissues and organs, causing inflammation and damage.

Symptoms of lupus can vary greatly from person to person and may come and go. Some common symptoms include:

  • Fatigue
  • Joint pain, stiffness, and swelling
  • Skin lesions that appear or worsen with sun exposure (photosensitivity)
  • Fingers and toes that turn white or blue when exposed to cold or during stressful periods (Raynaud’s phenomenon)
  • Shortness of breath
  • Chest pain
  • Dry eyes
  • Headaches, confusion, and memory loss

What is sepsis?

Sepsis is a potentially life-threatening condition that occurs when the body’s response to an infection injures its own tissues and organs. Instead of localizing a response to a particular site of infection, the body releases immune chemicals into the blood that trigger widespread inflammation, leading to blood clotting, impaired blood flow, and potentially organ failure.

Symptoms of sepsis may include:

  • Fever or hypothermia
  • Heart rate higher than 90 beats a minute
  • Breathing rate higher than 20 breaths a minute
  • Probable or confirmed infection
  • Altered mental status
  • Edema (swelling)
  • High blood glucose without diabetes

South West News Service writer Mark Waghorn contributed to this report.

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