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.

中文翻译：

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慢性吸烟者和湿鼻烟使用者炎症和免疫反应生物标志物的差异

背景吸烟是癌症和其他疾病的主要危险因素。虽然吸烟会诱发慢性炎症和异常免疫反应，但无烟烟草制品 (STP) 对免疫反应的影响尚不清楚。在这里，我们评估了与吸烟者 (SMK)、湿鼻烟消费者 (MSC) 和非烟草消费者 (NTC) 的免疫调节相关的标志物，以更好地了解长期吸烟的影响。材料和方法 通过流式细胞术在来自 SMK（n = 40）、MSC（n = 40）和 NTC（n = 40）的外周血单核细胞 (PBMC) 中测量了几种与免疫调节相关的标志物。结果 相对于 NTC，SMK 中有 7 个标记被显着抑制，而在 MSC 中，只有 1 个标记被显着抑制。在逻辑回归模型中，标志物包括颗粒酶 B+淋巴细胞，穿孔素 + 淋巴细胞、颗粒酶 B + CD8 + T 细胞和 KLRB1 + CD8 + T 细胞仍然是对三个队列进行分类的统计学显着预测因子。此外，相对于MSC，SMK中的细胞表面受体信号通路和细胞-细胞信号传导过程被下调；与 MSC 相比，SMK 中趋化性和 LPS 介导的信号通路上调。构建了测试标记的网络以可视化 SMK 中相对于 MSC 的免疫抑制。结论 与吸烟相比，使用湿鼻烟与炎症和免疫功能生物标志物的干扰显着减少有关。影响 这项工作确定了几个关键的免疫生物标志物，这些生物标志物将长期吸烟与使用湿鼻烟的影响区分开来。此外，