New research shows that smoking alters the immune system even years after quitting.

In this study, current smokers experienced a stronger inflammatory response after exposure to certain bacteria, which quickly disappeared when they quit smoking. In contrast, tobacco’s effects on T-cell responses persist years after people quit smoking.

People vary greatly in their immune responses, with age, gender and genetic factors playing important roles in this internal variability, but there are other external factors that can alter defenses. However, the variables that mediate such differences in cytokine secretion (a critical component of the host response to immunological challenges) remain poorly understood.

To this end, the researchers analyzed 136 variables and identified smoking, latent cytomegalovirus (CMV) infection and body mass index as the main factors influencing variability in cytokine response, with effects comparable in magnitude to age, sex and genetics.

Thus, they found that smoking is one of the environmental factors that most influences both the innate and adaptive immune responses. In particular, its effects on innate responses are rapidly lost after smoking cessation and are specifically associated with plasma CEACAM6 levels, whereas its effects on adaptive responses persist long after people quit smoking and are associated with epigenetic memory.

The results identify three new variables associated with variability in cytokine secretion and reveal the role of smoking in the short- and long-term regulation of immune responses. These findings have potential clinical implications for the risk of developing infections, cancer, or autoimmune diseases.

To reach this conclusion, experts collected 1,000 human samples from the Milieu Intérieur cohort. Donors were required to have no history or evidence of serious, chronic or recurrent medical conditions, neurological or psychiatric disorders, alcohol abuse, recent drug use, recent vaccine administration, and recent use of immunomodulatory agents.

To identify novel environmental factors associated with variability in response to immune stimulation, researchers focused on the secretion of cytokine proteins as a phenotype of the immune response, including the concentrations of 13 cytokines relevant to disease and medicine (CXCL5, CSF2, IFN, IL-1 , TNF, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17 and IL-23).

Stimulants are divided into four categories: microbial (Bacillus Calmette-Guerin (BCG), E. coli, lipopolysaccharide (LPS) and Candida albicans (C. albicans) and viral (influenza and polyinosinic acid-polycytidylic acid (poly I:C)), agents that are predominantly recognized by receptors on innate immune cells; T-cell activators (staphylococcal enterotoxin B superantigen (SEB) and anti-CD3 and anti-CD28 antibodies (anti-CD3 + CD28)) that induce adaptive immune responses and cytokines (TNF, IL-1 and IFN).

To assess the biological impact of smoking on cytokine secretion, they plotted effect sizes for smoking variables from linear models. Thus, they observed that smoking now influences immune responses, as tobacco is associated with stronger induction of the cytokine CXCL5 after E. coli stimulation and stronger induction of IL-2 and IL-13 after SEB stimulation. Variables related to smoking (number of years of smoking, number of years since last smoking, and total number of cigarettes smoked) showed a consistent association.

It also highlights that, unlike current smokers, former smokers do not show a significant increase in CXCL5 secretion after innate immune stimulation, while they do show an increase in IL-2 and IL-13 secretion after adaptive immune stimulation compared to humans. who have never smoked.

In summary, smoking, latent CMV infection, and body mass index, in addition to age, sex, genetic variations, DNA methylation levels, and immune cell subsets, have been shown to be variables more associated with changes in cytokine secretion following immunological challenge. .