Transitioning to e-cigarettes restores the immune response to house dust mite in cigarette smoked mice.

Abstract

Since the introduction of electronic cigarettes to the US market, e-cigarettes have been posited as a safe alternative to combustible cigarettes. We developed a preclinical animal model to determine whether transitioning to e-cigarette use after up to 16 weeks of daily exposure to combustible cigarette smoke (CS) could restore normal lung immune responsiveness to house dust mites (HDM). In these studies, CS exposed animals were randomly assigned to 6 groups. (1) CS-CS mice continued combustible cigarette exposure for an additional 7 or 16 weeks, and (2) CS-recovery mice were removed from cigarette smoking where they recovered without intervention. (3) CS-carrier mice transitioned to vaporized propylene glycol (30%) with vegetable glycerol (70%) (i.e. carrier). (4) CS-salt mice transitioned to e-vapor exposure containing nicotine salt (liquid nicotine in benzoic acid + carrier), and (5) CS-base mice transitioned to daily exposures to liquid nicotine + carrier containing e-vapors. (6) Room air exposed mice, that were not smoked or exposed to e-cigarette vapors, were included as controls. We hypothesized that transitioning from CS to either of the three e-cigarette exposures (base, salt or carrier) would restore eosinophil influx into the airways following intranasal HDM administration. Here we report that shorter (7 week) e-vapor exposure containing salt, base or carrier led to significant eosinophil responses following HDM challenge. In the 16-week model, CS-base and CS-salt exposed animals did not regain their HDM responsiveness when compared to controls. CS-carrier mice did regain partial responses to HDM at 16 weeks as indicated by an increase in eosinophils compared to control mice. Lung resident lymphoid cells support the influx of eosinophils following allergen exposure. As such we measured total T cells, B cells and group 2 innate lymphoid cells (ILC2) in the lungs of each of the treatment groups. ILC2 and CD4+ T cells were reduced, and B cells were increased in the lungs of CS mice compared to controls. Numerically, the transition to nicotine-salt increased the CD3+ T cell response but transitioning to the nicotine-base significantly reduced CD19 B cells. Additional studies showed that GM-CSF protein was increased in cultured ILC and in whole lung tissues of control mice compared to CS-carrier mice indicating plasticity of the ILC2 population. RNA microarray analyses identified significant increases in GM-CSF, CCL17 and CCL24 transcripts in alveolar macrophages following the transition from CS to carrier compared to control mice. In summary, the immunosuppressive effects of CS may be restored following short-term use of e-cigarettes, but chronic use of e-cigarettes may blunt pulmonary immunity similarly to traditional cigarette smoke.