Tattooing may trigger localised damage to the immune system

Tattoo ink collects in the lymph nodes and affects the immune system, causing potentially lifelong changes in the body's disease-fighting mechanisms.

This was the conclusion of a mouse study in which tattooed animals experienced chronic inflammation of ink-pigmented lymph nodes and altered antibody responses to vaccines. Human lymph nodes in tattooed people showed similar inflammation and coloration even years after people received tattoos.

The results suggest that tattoos may be associated with a higher risk of disease and more research is needed. Santiago Gonzalez at the University of Lugano in Switzerland.

“When you get a tattoo, you're actually injecting ink into your body,” he says. “It's not just a cosmetic effect on the skin; there are also effects on the immune system. The problem is that in the long term, inflammation eventually depletes the immune system, and then you have an increased risk of getting infections or certain types of cancer. So there are a lot of open questions that need further study.”

Tattoo has become a global trend. Between 30 and 40 percent of people in Europe and the US have at least one tattoo. Gonzalez is not among them, although he appreciates tattoos as an art form. “I think aesthetically they are beautiful,” he says. But scientists have relatively little information about long-term health effects of the tattoo processespecially in terms of how tattoos affect the immune system.

Gonzalez says he and his colleagues were working on an unrelated research project on inflammation in mice when they realized the animals were developing “crazy inflammatory reactions” after they were given small identification tattoos. Intrigued, they decided to investigate further.

The researchers used standard commercial inks in black, red and green to tattoo a 25-square-millimeter patch of skin on the hind legs of dozens of mice. Using special imaging equipment, they observed how the ink moved across lymphatic vessels inside the leg to nearby lymph nodes almost immediately, often within minutes.

There, the team saw that macrophages—immune cells that clear away debris, pathogens, and dead cells—took up the ink, staining the nodules and causing acute inflammation. Within about 24 hours, these macrophages died, releasing ink that was then taken up by other macrophages. They too died and released ink, which was absorbed by other macrophages, creating a cycle of noticeable chronic inflammation that lasted long after the tattoo site itself had healed.

By the end of the experiment, two months after tattooing, the mice's lymph nodes still had five times normal levels of inflammatory markers, Gonzalez said.

To find out whether this inflammation affected immune function, the researchers then injected the vaccines directly into the tattooed skin. The antibody response of tattooed mice to the Covid-19 mRNA vaccine was noticeably weaker than that of control mice, but their response to the flu vaccine was actually stronger.

Further analyzes showed that the macrophages in the lymph nodes of the tattooed mice were so filled with ink that they took up less of the Covid-19 vaccine, which, like an mRNA vaccine, needs to be processed by macrophages to function. However, in the case of the protein-based flu vaccine, inflammation increased the antibody response, possibly because more immune cells were attracted to the tattoo site. “It could really depend on the type of vaccine,” Gonzalez says.

Finally, the team studied a small set of lymph node biopsies from people who had tattoos in the areas adjacent to the nodes. Even two years after tattooing, the nodes still contained visible pigment packed into the same macrophages seen in the mouse study. “Their lymph nodes were completely filled with ink,” Gonzalez says.

It's important to note that the ink will likely remain in the knots for life, he adds, even if people have had their tattoos removed. “You can remove ink from the skin, but you cannot remove it from the lymph nodes,” he says.

The results shed important light on long-suspected links between tattoos and the immune system, he says. Christel Nielsen at Lund University in Sweden. Last month, she and her colleagues published a study reporting increased risk of melanoma in tattooed people. She thought her team's findings might be due to increased inflammation in the lymph nodes. “This study provides compelling evidence that this is indeed the case,” she says. “This is a significant advance in our understanding of how tattoos may be linked to disease.”

For Michael Gyulbudaghyan The work, carried out at the German Federal Institute for Risk Assessment in Berlin, provides a much clearer picture of how tattoo pigments interact with the immune system. Despite this, he emphasizes that the results of the study in mice do not necessarily reflect exactly what happens in humans, especially because human skin is significantly different from mouse skin. “The significance to human health, especially after the wound has fully healed, requires further study,” he says.