Smoking Has Long-Term Effects on Your Immune System, New Study Finds

Smoking shapes your adaptive immune system into something more overreactive and pro-inflammatory even long after you quit.

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Smoking does not do a body good. We’ve known this universally acknowledged truth for at least the past 60 years. Still, researchers are constantly finding new ways that it harms our health. In a study out this week in Nature, scientists detail how smoking influences the immune system, revealing how it affects a person’s pathogen-fighting abilities even years after they’ve quit.

Researchers in France exposed immune system-related cells collected from blood samples of 1,000 healthy individuals to various molecules associated with bacterial and viral infections. They measured levels of immune system-related chemicals released by these cells and correlated those values to an individual’s personal history. The researchers found that smoking had the greatest influence on the immune response compared to other environmental factors. It particularly seemed to affect adaptive (or acquired) immunity, shaping it into something more overreactive and pro-inflammatory. Comparing current and past smokers to non-smokers, these changes seem to endure for many years even after one quits smoking and tied, yet again, to pernicious genetic modifications.

“The major discovery of our study is that smoking has short-term but also long-term consequences on an individual’s immunity,” Violaine Saint-André, the paper’s first author and a computational biologist at the Pasteur Institute in Paris, told reporters during a press briefing on Tuesday. “The key message, especially to the youth, is that there seems to be a significant interest for long-term immunity to never start smoking.”

Rewiring genes

It’s well known that smoking, as well as vaping, can harm the immune system. For example, some studies have found that nicotine, the addictive substance found in all tobacco products, paralyzes the immune system by coaxing immune cells to tamp down on protective inflammatory responses and even promote tumor growth.

In the new study, the researchers hadn’t set out to study smoking’s impact on the immune system specifically, although they were greatly interested in sussing out that relationship. The undertaking is part of a large-scale project in France called the Milieu Intérieur Consortium to dip into what factors — whether age, gender, body fat content, or environmental exposures — underlie the diversity of immune responses among healthy people.

Initiated in September 2012, the consortium enrolled 1,000 healthy adults split evenly between those who biologically identified as men and women between the ages of 20 and 69. These individuals were all of Western European descent. Blood, skin, poop, and other biological samples were collected; participants filled out surveys about their lifestyle (which included smoking habits like total number of cigarettes smoked daily) and personal and family medical history. As part of the consortium’s overarching research efforts, participants were followed up 10 years later. Pregnant individuals and those approaching menopause were excluded to avoid the challenging aspect of hormonal fluctuations.

Saint-André and her colleagues took the blood samples collected, put all the cells contained in those samples (which included cells related to the immune system) in Petri dishes, and exposed them to 11 different proteins and other molecules associated with bacterial and viral infections. They then measured levels of cytokines, proteins integral to the immune system that help regulate and control inflammation, released by these cells. To associate the results with environmental factors, the researchers turned to the surveys the participants had filled out to see what lifestyle choices or medical history stuck out the most.

“We identified three main factors that were explaining variability in cytokine response in addition to age, sex, and genetics,” Darragh Duffy, the paper’s senior author and an immunologist at the Pasteur Institute, told reporters in the press briefing. “Those three environmental factors were smoking, BMI [body mass index], and cytomegalovirus latent infection – that’s a herpes virus that is common in the population.”

While smoking affected both arms of the immune system — innate (of the body’s first line of defense) and adaptive immunity — the effects were more striking for the latter. The researchers saw more pro-inflammatory cytokines corresponding to B cells, which make antibodies, and T cells, which identify and protect the body from infection by activating other immune cells or killing infected cells themselves.

The exact mechanism underlying the harmful, overactive adaptive immune response appeared to be due to alterations to the epigenome, or the chemical modifications on our DNA that influence which genes are turned on or off. More of those epigenetic changes were observed among current and past smokers versus non-smokers, particularly among genes involved in biochemical signaling processes and metabolism.

A silver lining is that these undesirable modifications dissipate over time once you stop smoking, although it may take much longer for adaptive immunity to recuperate.

“Clearly for innate immune stimulation, once individuals stop smoking, they retrieve the cytokine behavior of non-smokers,” said Saint-André. “For adaptive immune stimulation, it may take some years” because of lingering epigenetic alterations.

Future research

These findings corroborate other studies showing tobacco smoke interferes with T cell immunity as well as B cell function. A 2014 study published in The Journal of Immunology found that adaptive immunity was impaired for weeks in mice after exposure to smoke.

Saint-André and Duffy, however, caution there are some limitations to their study, such as extrapolating a phenomenon observed in Petri dishes as replicating what we would expect to see in the body, and the challenge of generalizing these findings to a diverse population since participants are of European descent.

These findings are also based on healthy individuals, so it’s hard to say how smoking’s lasting effect on adaptive immunity plays into one’s vulnerability during an infection or other inflammatory diseases. Duffy said that’s a line of research he and his colleagues are investigating using participants from the Milieu Intérieur Consortium.

The researchers are also unsure which exact substances in tobacco smoke are responsible — the study only correlated cytokine levels with smoking history. But Duffy said that a gene called aryl hydrocarbon receptor repressor (or AhRR), which is involved in a metabolic pathway cells use to process toxins, may be at play here.

“[The gene] has been associated with smoking before — it’s actually the toxins within cigarette smoke that are impacting the metabolism of cells, which is kind of known, but it wasn’t known that it was also with T cells,” said Duffy. “So that’s what we think is the link between actual components in cigarette smoke and the impact on the immune system.”

While this research remains ongoing, it adds to the growing mountain of evidence of how bad smoking is for you, and that a whiff of nicotine isn’t worth putting your immune system on the line.

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