Comparative study of the effects of cigarette smoke versus next-generation tobacco and nicotine product extracts on inflammatory biomarkers of human monocytes

Abstract

Monocytes exhibiting a pro-inflammatory phenotype play a key role in adhesion and development of atherosclerotic plaques. As an alternative to smoking, next-generation tobacco and nicotine products (NGP) are now widely used. However, little is known about their pro-inflammatory effects on monocytes. We investigated cell viability, anti-oxidant and pro-inflammatory gene and protein expression in THP-1 monocytes after exposure to aqueous smoke extracts (AqE) of a heated tobacco product (HTP), an electronic cigarette (e-cig), a conventional cigarette (3R4F) and pure nicotine (nic). Treatment with 3R4F reduced cell viability in a dose-dependent manner, whereas exposure to alternative smoking products showed no difference to control. At the highest non-lethal dose of 3R4F (20%), the following notable mRNA expression changes were observed for 3R4F, HTP, and e-cig respectively, relative to control; HMOX1 (6-fold, < 2-fold, < 2-fold), NQO1 (3.5-fold, < 2-fold, < 2-fold), CCL2 (4-fold, 3.5-fold, 2.5-fold), IL1B (4-fold, 3-fold, < 2-fold), IL8 (5-fold, 2-fold, 2-fold), TNF (2-fold, 2-fold, < 2-fold) and ICAM1 was below the 2-fold threshold for all products. With respect to protein expression, IL1B (3-fold, < 2-fold, < 2-fold) and IL8 (3.5-fold, 2-fold, 2-fold) were elevated over the 2-fold threshold, whereas CCL2, TNF, and ICAM1 were below 2-fold expression for all products. At higher doses, greater inductions were observed with all extracts; however, NGP responses were typically lower than 3R4F. In conclusion, anti-oxidative and pro-inflammatory processes were activated by all products. NGPs overall showed lower responses relative to controls than THP-1 cells exposed to 3R4F AqE.

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

“…This section will discuss those studies that utilized cells derived from the cardiovascular system. Four articles were identified that utilized bubbled liquid extracts to compare the in vitro effects of HTPs with cigarettes in cell lines derived from the cardiovascular system [ 40 , 87 - 90 ]. As mentioned previously, when investigating cardiovascular endpoints, bubbled liquid extract exposure is more reflective of exposure to those constituents that are absorbed into the blood after product use and then maybe transported throughout the cardiovascular system.…”

“…In the fourth study, the effects of liquid extracts produced from the IQOS HTP on a human monocytic (THP-1) cell line were investigated [ 90 ]. Whole smoke/aerosol from the 3R4F Kentucky reference cigarette, IQOS HTP, and an EVP (Vype) were bubbled into the cell culture medium.…”