Differences in biomarkers of inflammation and immune responses in chronic smokers and moist snuff users

Cytokine. 2021 Jan:137:155299. doi: 10.1016/j.cyto.2020.155299. Epub 2020 Oct 1.

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.

Keywords: Immune surveillance: biomarkers of potential harm; Inflammation; Moist snuff; Smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood*
  • CD4 Antigens / blood
  • CD8 Antigens / blood
  • Chemokine CCL3 / blood
  • Cohort Studies
  • Humans
  • Immunity*
  • Inflammation / blood*
  • Inflammation / diagnosis
  • Inflammation / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily B / blood
  • Non-Smokers / statistics & numerical data*
  • Protein Interaction Maps
  • Risk Factors
  • Smokers / statistics & numerical data*
  • Tobacco, Smokeless / statistics & numerical data*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Biomarkers
  • CD4 Antigens
  • CD8 Antigens
  • Chemokine CCL3
  • NK Cell Lectin-Like Receptor Subfamily B
  • Tumor Necrosis Factor-alpha