Tattooing may trigger localised damage to the immune system

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

That is the conclusion of a study in mice, in which tattooed animals showed chronic inflammation in their lymph nodes – which were pigmented with the ink – and had altered antibody responses to vaccines. Human lymph nodes from tattooed individuals had similar inflammation and colouring, even years after people received their tattoos.

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

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

Tattooing has become a global trend. Between 30 and 40 per cent of people in Europe and the US have at least one tattoo. González isn’t among them, although he appreciates tattoos as an art form. “I think that, aesthetically, they are beautiful,” he says. But scientists have relatively little information about long-term health effects of the tattooing process, especially in terms of 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 realised that the animals developed “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-millimetre patch of skin on the hind feet of dozens of mice. With specialised imaging equipment, they watched the ink travel along the lymphatic vessels inside the leg up to the nearby lymph nodes almost immediately, often within minutes.

There, the team saw that macrophages – immune cells that clean up debris, pathogens and dead cells – captured the ink, tinting the nodes and provoking acute inflammation. Within about 24 hours, those macrophages died, releasing the ink, which then got captured by other macrophages. Those, too, would die and release ink, which would get taken up by yet other macrophages – creating a cycle of prominent, chronic inflammation that lasted well after the tattoo site itself had healed.

By 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, says González.

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

Further analyses showed that the lymph node macrophages of tattooed mice were so full of ink that they captured less of the covid-19 vaccine – which, as an mRNA vaccine, needs processing by macrophages to be functional. For the protein-based influenza vaccine, however, inflammation boosted the antibody response, perhaps because there were more immune cells recruited to the tattooed site. “It may really depend on the type of vaccine,” says González.

Finally, the team examined a small set of lymph node biopsies from people who had been tattooed in regions near the nodes. Even two years after tattooing, the nodes still contained visible pigment, packed into the same kinds of macrophages as seen in the mouse study. “Their lymph nodes were completely full with ink,” says González.

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

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

For Michael Giulbudagian at 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. Even so, he stresses that the findings from the mouse study might not necessarily reflect exactly what is going on in humans, particularly since human skin is significantly different from mouse skin. “The relevance for human health, in particular after the complete healing of the wound, must be further investigated,” he says.