Your Tattoo Has Opinions About Your Flu and Covid Shot

Thinking of getting a tattoo? New research prompts us to think of one more important question before deciding when to get tattooed: Are you due for a seasonal flu or COVID shot anytime soon?

If yes, you may want to time things carefully.

A study published in PNAS last November suggests tattoo ink might interact with vaccines in unexpected ways. The research was conducted in mice, with some experiments in human cells. Still, the findings are striking: tattoos reduced antibody responses to COVID-19 vaccines but enhanced responses to flu vaccines, depending on ink color and timing.

Many of us have tattoos or know someone who does. I keep going back and forth on which designs and placements for years, but I still haven't pulled the trigger.  Part of it is the pain (yes, I know that sounds silly to the experienced!)

My fear of pain seemed rational enough. Tattoos break the skin barrier, activating sensory nerves and triggering mild inflammation as immune cells rush to repair the damage. I assumed they heal quickly and return to normal, just like my ear piercings did. After all, tattooing is incredibly common (32% of Americans have at least 1 tattoo- link), and has been practiced across cultures for millennia.

What I did not comprehend: tattoo ink can alter your immune response over the long term. And this can influence vaccine effectiveness.  

This new study, published in PNAS, tracked what happens when commercial tattoo ink meets the immune system. Researchers tattooed mice with black, red, and green inks, then vaccinated them either 2 days or 2 months later with either the COVID-19 mRNA vaccine or an inactivated flu vaccine.

Important caveat: This was primarily a mouse study, though the team also tested human immune cells in the lab and examined lymph nodes from tattooed people. The findings don't mean you should panic about your tattoos, but they do suggest we need stricter regulations on tattoo ink ingredients and clinical trials to determine whether these effects occur in humans.

Tattoo Ink and Regulations

So why are we hearing about this now? Aren't there any existing regulations over tattooing? 

These were the immediate questions that sprang to mind as I saw the title and abstract of this manuscript. So I went looking, and here's what I found. Turns out, the FDA does not approve tattoo inks but only monitors problems and coordinates voluntary recalls.  Under the Federal Food, Drug, and Cosmetic Act, tattoos are considered cosmetics, whereas the pigments used in the inks are color additives that require premarket approval. However, the FDA has chosen not to exercise its regulatory authority over tattoo ink pigments, citing competing public health priorities and a lack of prior evidence of safety problems associated with these pigments.

As a result, no tattoo ink has ever been FDA-approved for injection into the human skin.

But is it true that there haven't been safety problems associated with tattoos yet? Actually, no. The FDA's own website lists adverse effects and recalls in 2003, 2004, 2011, 2012, 2014, 2017, and 2019 in the US. Most of these were due to bacterial contamination, but some involved allergic reactions and other complications.

What I found more alarming: tattoo inks contain pigments originally designed for printer toners and car paint- industrial chemicals never intended for injection into human tissue. Surely that should raise a huge red flag, right? 

And there's another gap: Even basic guidance on vaccine-tattoo timing is murky. Medical experts generally recommend avoiding vaccination over a fresh tattoo (less than 1 month old) and avoiding tattooing over a recent vaccination site. The reasoning is practical- both procedures can cause pain and inflammation, so it's difficult to determine which is causing problems if they happen simultaneously. But these are informal recommendations, not official guidelines. Until this study, no one had tested whether the timing matters for vaccine effectiveness.

Given these voids in our understanding, these researchers decided to investigate what happens when tattoo ink meets vaccines.

Study Design

Researchers tattooed the footpads of mice with either saline (control group) or inks containing commercially available black, green, or red dyes from a major tattoo ink supplier. The mice were then vaccinated with either the SARS-CoV-2 mRNA vaccine or UV-inactivated influenza vaccine 2 days or 2 months after tattooing to evaluate short-term and long-term effects on immune responses. They measured antibody levels (IgG and IgM) as indicators of vaccine effectiveness- higher levels mean better protection.

When tattooed mice were vaccinated with SARS-CoV2 mRNA vaccine, all groups, regardless of ink color, showed reduced anti-RBD IgG levels- antibodies that recognize the RBD spike protein on the virus. This was consistent at both 2 days and 2 months post-tattooing, demonstrating persistent immune impairment. These results demonstrate for the first time that tattoo ink reduces antibody responses to SARS-CoV-2 mRNA vaccines in mouse models.

An in-depth investigation concluded that the reduced antibody levels were due to fewer functional medullary macrophages- specialized immune cells in the body, whose function was compromised in the tattooed groups. As a result, ink-carrying macrophages showed reduced uptake of the vaccine mRNA and decreased spike protein expression, thereby weakening the signal that triggers robust antibody production.

However, the story flipped when tattooed mice were vaccinated with a UV-inactivated influenza vaccine. In this case, black and red ink groups showed increased antibody responses (IgG and IgM levels) to the vaccine, although responses varied by ink color and vaccination timing. In this case, the ink acted as a stimulus, that boosts vaccine responses.

Ink and Macrophages - A Toxic Story

A closer look at what really happens after tattooing gave the researchers a better idea of the cells involved: medullary macrophages. When we get tattoos, not all of it stays on the skin. Some leftover ink is captured by macrophages that move toward the nearest lymph node, where they attempt to trigger an immune response.  However, some colors, especially red pigment, are highly toxic to macrophages, causing their death in the lymph nodes. The green dye was found to be the least toxic among those tested.

Cell death is often accompanied by inflammation, which signals the body's cleanup system to the site to contain the perceived threat. This resulted in a significant increase in the number of cells at the inflamed lymph node - B-cells, T-cells, NK-cells, and Dendritic Cells. Researchers observed that inflammation persisted well into two months after tattooing. These findings in mice were also seen in human lymph node biopsy samples from tattooed individuals.

Takeaways

This is the first comprehensive study examining how tattoo ink affects vaccine responses. The effects were found to be vaccine-specific, with a decrease in mRNA vaccine responses but an enhancement of whole-cell inactivated flu vaccines. Most importantly, the observed effects were relatively long-lasting (2 months post-tattoo). It's interesting to see that different inks elicited varying levels of cell death and inflammation, with red dyes being more reactive than others. Tests with human cells and biopsy samples show that the observed effects are also relevant to humans.

Important Caveats

This is an animal study, performed in mice. Although supported by a few in vitro and ex vivo studies using human-derived samples, the observations should be interpreted with caution. Let's take a look at a list of potential confounders.

Size of tattoo: The study tested small tattoos on the footpad of mice, which is difficult to directly translate to humans. We do not yet know whether the size of the tattoo matters.

Location of tattoos: This study cautions against vaccinating over a tattooed limb, but whether tattoos in the vicinity also affect vaccine responses remains unclear.

Vaccine dose: Mice received vaccine doses scaled to their size, but the tattoo ink-to-body-mass ratio may differ significantly from that in humans.

Vaccine formulation: The current study tested only two vaccine types. It is unclear how other vaccines (e.g., tetanus, hepatitis, etc.) will work on tattooed individuals.

The full effects of tattoos on lymph node inflammation and subsequent vaccine responses are currently unpredictable, although this study's results suggest potential risks. This research highlights the need for stricter regulation of tattoo ink ingredients and clinical trials to determine whether these immune effects occur in humans.

So, should you cancel your tattoo appointment? Not necessarily. But if you're planning both a tattoo and a vaccine, spacing them 2-4 weeks apart seems like a reasonable precaution until we know more.

As for me? By the time I finally decide on a design (yes, still deliberating), I'm hoping regulations will have caught up with the science. So I can get tattooed knowing the ink has actually been safety-tested, not just repurposed from printer toner.