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Smoking Activates Neutrophils, Possibly Boosting CVD and Cancer Risk
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18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York
Mark Mascolini
Older smokers taking antiretrovirals had signals of neutrophil activation in a small French study [1]. ACTIVIH researchers in Montpellier and Nimes believe activated neutrophils may play a role in the pathogenesis of cardiovascular disease (CVD) and cancer.
The ACTIVIH team reminded colleagues that immune activation persists in HIV-positive people responding well to antiretroviral therapy (ART) and contributes to an array of metabolic diseases and some cancers. The impact of smoking on some of these same diseases is well appreciated. Because neutrophils contribute to immune activation, the researchers hypothesized that smoking adds to comorbidity risk by spurring neutrophil activation.
ACTIVIH includes 120 antiretroviral-treated people older than 45 with a CD4 count above 200 and a viral load below 50 copies for at least 24 months [2]. This cross-sectional analysis involved 69 virologically suppressed people with a nadir CD4 count below 350 and a viral load below 50 copies for at least 2 years. The investigators assessed 68 markers of immune activation and 3 neutrophil activation markers: CD64, CD62L, and PDL1.
Fifty-five of the 69 study participants (80%) were men, 30% were smokers, and 22% were former smokers. Their age averaged 58 years and they had taken ART for an average 16 years. Nadir CD4 count averaged 187, current CD4 count 714, and CD4/CD8 ratio 0.994.
The researchers found only one association between smoking and an array of standard immune activation markers: expression of HLA-DR on CD8 cells (P = 0.029). Smoking was significantly associated with expression of the neutrophil activation marker CD62L, which was overexpressed in current smokers (5.021 +/- 0.894) compared with former smokers (4.938 +/- 0.864) and nonsmokers (4.152 +/- 1.126) (P = 0.022). The ACTIVIH team saw a trend for a positive correlation between number of cigarettes smoked daily and CD62L expression on neutrophils (r = 0.34, P = 0.09).
The investigators also found a trend between higher PDL1 expression on neutrophils in smokers versus former smokers or nonsmokers (P = 0.09). And PDL1 expression correlated significantly with number of cigarettes smoked daily (r = 0.405, P = 0.04).
The researchers concluded that smoking is associated with expression of CD62L on neutrophils, while number of daily cigarettes correlates with PDL1 density on neutrophils. They proposed that smoking "might fuel chronic neutrophil activation-mediated morbidities such as atherothrombosis and cancer."
References
1. Psomas C, Tuaillon E, Barbas S, et al. Tobacco smoking contributes to neutrophil activation in people living with HIV: the ACTIVIH study. 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York. Abstract O09.
2. Psomas C, Younas M, Reynes C, et al. One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study. EBioMedicine. 2016;8:265-276. http://www.ebiomedicine.com/article/S2352-3964(16)30191-8/abstract
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