No Smoke without Fire: The Blazing Effects of Smoking on the Immune System

With 2024 coming to a close and a new year on the horizon, many people begin setting New Year’s resolutions to motivate themselves to break habits and kickstart healthier routines. A prominent resolution that appears year after year is the pledge to quit smoking, which often also ties in with other key promises, such as getting healthier and saving money.

However, kicking this addiction is no mean feat. So, if you’re looking for a little extra inspiration to help you quit smoking, look no further! In this blog, we discuss a new study highlighting the negative impact of smoking on the immune system.

The Smoking Gun

Globally, around 23% of the population has an addiction to cigarettes, which is linked to the development of problems such as coronary artery disease, cancers in various organs, decreased reproductive health, and chronic obstructive pulmonary disease to name a few (Aslam et al. 2024). Shockingly, an estimated 480,000 deaths per year in the U.S. are associated with smoking. If that alone isn’t enough to put you off, let’s dive a little deeper.

The effects of smoking on the immune system are numerous and have been well documented. For example, a recent study by Saint-André et al. (2024) aimed to pinpoint the main variables that impact an individual’s responsiveness to immune challenges. The researchers used samples from the Milieu Intérieur cohort, which is composed of 1,000 healthy individuals consisting of 100 women and 100 men from each decade between the ages of 20 and 69.

To assess the impact of different factors on the immune response, blood samples were stimulated with a variety of immune triggers, which were broadly classified into four categories: microbial stimulants, viral stimulants, T cell activators, and cytokines. These can each provoke different flavors of immune activation, thus enabling the investigation of the degree of impact on both innate and adaptive immune responses. Following stimulation, the production of 13 disease-relevant cytokines was measured to quantify the robustness of the response.

Out of the 136 factors surveyed, smoking was one of the most prominent environmental factors associated with variability in cytokine release among otherwise healthy individuals, impacting both innate and adaptive immunity.

Specifically, smoking was associated with a significantly higher production of the neutrophil-recruiting chemokine CXCL5 following E. coli stimulation. This is in line with previous studies stating that smoking exacerbates lung inflammation via the accumulation of neutrophils (Lugade et al. 2015).

In addition, smoking was linked to a greater induction of the cytokines interleukin (IL-)2 and IL-13 after stimulation with the T cell activator Staphylococcus aureus enterotoxin B superantigen (SEB). IL-13, in particular, has been coupled to increased sensitivity to lung irritants and alterations in T helper 2 (Th2)-mediated immune responses provoked by smoking (Cooper et al. 2010, Mertens et al. 2017).

So, with the immune system up in smoke, can cessation of this habit reverse these effects? Or is the damage done?

The Slow Burn

To evaluate the efficacy of quitting smoking on restoring the normal functioning of the immune system, the researchers compared the immune response to different triggers in past and current smokers.

Interestingly, individuals who had smoked in the past and successfully quit showed no significant increase in CXCL5 production following innate stimulation compared to non-smokers, in contrast to their active smoking counterparts.

However, it appears that the adaptive immune system doesn’t forgive so easily. In past smokers, IL-2 and IL-13 secretion following adaptive immune stimulation remained dramatically increased in comparison to non-smokers, on level with that of current smokers, despite kicking the habit. Cytokine production also correlated with the number of years an individual smoked, for both current and past smokers. So, while the innate immune system bounces back quickly, the effects of smoking on the adaptive immune response persist.

But how exactly does smoking exert these long-term changes on the adaptive immune system? To address this question, the team decided to look into possible epigenetic changes — which alter how the genome is regulated without changing the DNA itself — that could impact cytokine production.

DNA methylation is a major player in epigenetics. The addition of methyl groups to DNA reduces its accessibility to transcription factors, thus repressing gene transcription (Moore et al. 2013). Current smokers were reported to have a state of DNA hypomethylation compared to non-smokers, with past smokers sitting at an intermediate state between the two, which likely accounts for the abnormal rise in cytokine levels in this group.

But don’t fret! There’s still hope for ex-smokers. The number of years since a person had quit smoking was found to positively correlate with the level of DNA methylation, indicating that the immune system can slowly but surely reset itself.

So, if you’re looking for some motivation to quit smoking, the research shows that this habit wreaks havoc on your immune response but quitting sooner rather than later gives your immune system the chance to catch its breath.