Tattooing can trigger localized damage to the immune system

Tattoo ink builds up in lymph nodes and interferes with the immune system, causing potentially permanent changes to the body’s disease-fighting mechanisms.

That’s the conclusion of a study in mice, in which tattooed animals had chronic inflammation of their lymph nodes – which were pigmented by the ink – and had an impaired antibody response to vaccines. The human lymph nodes of people with tattoos showed similar inflammation and discoloration, even years after the people received their tattoos.

The findings suggest that tattoos may be associated with higher disease risks and that more research is needed, says Santiago González of the University of Lugano in Switzerland.

“When you tattoo, you’re injecting ink into your body,” he says. “It’s not just a cosmetic effect associated with the skin; there are effects on the immune system as well. The problem is that over the long term, inflammation ends up depleting the immune system and then you have a higher risk of getting infections or certain types of cancer. So there are a lot of open questions that need further study.”

Tattooing has become a global trend. Between 30 and 40 percent of Europeans and Americans have at least one tattoo. González is not one of them, although he appreciates tattoos as an art form. “I think, aesthetically, they are beautiful,” he says. But scientists have relatively little information about the long-term health effects of the tattooing process, particularly regarding how tattoos affect the immune system.

González 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 being given small tattoos for identification. Intrigued, they decided to investigate further.

The researchers used standard commercial inks in black, red and green to tattoo a 25 square millimeter area of ​​skin on the hind legs of dozens of mice. Using specialized imaging equipment, they watched the ink travel along the lymphatic vessels inside the leg to nearby lymph nodes almost immediately, often within minutes.

There, the team found that macrophages – immune cells that clean up debris, pathogens and dead cells – captured the ink, staining the lymph nodes and causing acute inflammation. Within about 24 hours, these macrophages died, releasing the ink, which was then captured by other macrophages. These, too, would die and release ink, which would be taken up by other macrophages, creating a cycle of significant chronic inflammation that lasted well after the tattoo site itself had healed.

At the end of the experiment, two months after tattooing, the mice’s lymph nodes still had levels of inflammatory markers up to five times higher than normal, González says.

To determine whether this inflammation affected immune function, the researchers then injected vaccines directly into the tattooed skin. The tattooed mice’s antibody response to an mRNA covid-19 vaccine was significantly weaker than that of control mice, but their response to a flu vaccine was actually stronger.

Further analysis showed that the macrophages in the lymph nodes of the tattooed mice were so full of ink that they captured less of the covid-19 vaccine – which, as an mRNA vaccine, requires macrophage processing to be functional. However, for the protein-based flu vaccine, inflammation boosted the antibody response, perhaps because there were more immune cells recruited to the tattooed site. “It can really depend on the type of vaccine,” says González.

Finally, the team looked at a small set of lymph node biopsies from people with tattoos in areas near the nodes. Even two years after tattooing, the lymph nodes still contained visible pigments, clustered in the same types of macrophages seen in the mouse study. “Their lymph nodes were completely filled with ink,” says González.

Importantly, the ink is likely to stay in the knots for a lifetime, he adds – even if people have their tattoos removed. “You can remove ink from the skin, but you can’t remove it from the lymph nodes,” he says.

These findings shed important light on long-suspected links between tattoos and the immune system, says Christel Nielsen of Lund University in Sweden. Last month, she and her colleagues published a study reporting an increased risk of melanoma in people with tattoos. She thought her team’s results 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 substantial advance in our understanding of how tattoos may be linked to disease.”

For Michael Giulbudagian of the German Federal Institute for Risk Assessment in Berlin, the work offers a much clearer picture of how tattoo pigments interact with the immune system. Still, he points out that the results of the mouse study don’t necessarily accurately reflect what happens in humans, especially since human skin is very different from mouse skin. “The relevance to human health, especially after the wound has fully healed, needs to be studied in more detail,” he says.