Differences in biomarkers of inflammation and immune responses in chronic smokers and moist snuff users. (January 2021) - Tran, Quynh T.
Graphical abstract: Highlights: Toxicants in cigarette smoke are drivers of smoking-related diseases such as cancer. Cigarette smoking impacts systemic immune responses, including immune surveillance. Several inflammation and immune markers are suppressed in smokers. Moist snuff users exhibit much reduced impact on inflammation and immune response. The biomarkers discussed in our work would be useful in tobacco product regulation. Abstract: Background: Cigarette smoking is a major risk factor for cancer and other diseases. While smoking induces chronic inflammation and aberrant immune responses, the effects of smokeless tobacco products (STPs) on immune responses is less clear. Here we evaluated markers related to immune regulation in smokers (SMK), moist snuff consumers (MSC) and non-tobacco consumers (NTC) to better understand the effects of chronic tobacco use. Materials and methods: Several markers associated with immune regulation were measured in peripheral blood mononuclear cells (PBMCs) from SMK (n = 40), MSC (n = 40), and NTC (n = 40) by flow cytometry. Results: Relative to NTC, seven markers were significantly suppressed in SMK, whereas in MSC, only one marker was significantly suppressed. In a logistic regression model, markers including granzyme B + lymphocytes, perforin + lymphocytes, granzyme B + CD8 + T cells, and KLRB1 + CD8 + T cells remained as statistically significant predictors for classifying the three cohorts. Further, cell-surface receptor signaling pathways and cell–cell signaling processes were downregulated in SMK relative to MSC; chemotaxis and LPS-mediated signaling pathways, were upregulated in SMK compared to MSC. A network of the tested markers was constructed to visualize the immunosuppression in SMK relative to MSC. Conclusion: Moist snuff consumption is associated with significantly fewer perturbations in inflammation and immune function biomarkers relative to smoking. Impact: This work identifies several key immunological biomarkers that differentiate the effects of chronic smoking from the use of moist snuff. Additionally, a molecular basis for aberrant immune responses that could render smokers more susceptible for infections and cancer is provided.