Mysterious Immune Protein IL-40 Found to Surge in COVID-19 Patients with Pneumonia-Like Symptoms
Nikhil Prasad Fact checked by:Thailand Medical News Team May 11, 2025 20 hours, 40 minutes ago
Medical News: A New Clue in COVID-19 Severity Found in a Little-Known Immune Molecule
A new study conducted by researchers from the Department of Immunology and the Department of Infectious Diseases and Clinical Microbiology at Gazi University Faculty of Medicine in Ankara, Türkiye, has revealed surprising insights into a little-known immune molecule called Interleukin-40, or IL-40, and its possible role in severe COVID-19 infections.
Mysterious Immune Protein IL-40 Found to Surge in COVID-19 Patients with Pneumonia Like Symptoms
The team analyzed blood samples from 60 COVID-19 patients—30 with mild symptoms and 30 with severe pneumonia—alongside 30 healthy volunteers. Their goal was to explore how levels of IL-40 changed with infection severity and whether this molecule played a role in the body’s immune response, especially in connection to IgA antibodies and a process known as NETosis. This
Medical News report uncovers how this mysterious protein could be a marker—or even a driver—of severe illness in COVID-19 patients.
What is IL-40 and Why It Matters
IL-40 is a recently discovered immune system protein linked to B-cells, especially those that produce IgA antibodies in mucous membranes like the lungs and gut. While its role in autoimmune diseases has been studied before, this is the first time scientists have looked at IL-40 levels in people infected with SARS-CoV-2.
Using high-tech laboratory tools like ELISA tests and nephelometry, the researchers measured IL-40 and IgA levels in all participants. They found that COVID-19 patients had significantly higher levels of IL-40 compared to healthy individuals—and the spike was far greater in those suffering from pneumonia. Interestingly, these high IL-40 levels closely matched a dramatic increase in IgA antibodies and several NETosis-related enzymes, including neutrophil elastase (NE), proteinase 3 (PR3), and myeloperoxidase (MPO).
The Dangerous Chain Reaction in Severe COVID-19
NETosis is a defense mechanism where immune cells release webs of proteins to trap and kill viruses. However, in COVID-19, excessive NETosis has been linked to severe inflammation and organ damage. The researchers discovered that IL-40 levels correlated strongly with NETosis activity, especially in patients with pneumonia, hinting at a dangerous cascade.
Patients with high IL-40 not only had more IgA but also showed much higher levels of NETosis markers in their blood. This suggests a possible loop: IL-40 boosts IgA, which in turn could trigger more NETosis, possibly worsening inflammation in the lungs.
The Link Between IL-40 and IgA Is Clearer Than Ever
The team performed statistical analyses and confirmed a strong correlation between IL-40 and IgA, especially in patients with pneumonia. While patients with mild symptoms had only moderate IL-40 and no significant rise in IgA, those with pneumonia showed dramatic increases in both. This finding s
uggests that IL-40 might play a key regulatory role in how the body generates IgA during infections.
What This Means for COVID-19 Patients and Future Research
The researchers believe that IL-40 may be a missing piece in understanding how the immune system overreacts during severe COVID-19 cases. They speculate that IL-40 may push the immune system to produce more IgA, which could then overstimulate processes like NETosis, leading to dangerous levels of inflammation in the lungs.
More importantly, these findings suggest that IL-40 could be explored as a potential biomarker to identify patients at risk of developing severe complications. Targeting IL-40 might even open new doors for therapies in both infectious and autoimmune diseases.
The study findings were published in the peer reviewed journal: PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0321578
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