Daily smoking is associated with circulating HGF, βNGF, CXCL9 and CXCL10

Abstract

Tobacco smoking is one of the major causes of lifestyle morbidity and mortality by causing cardiovascular disease, lung disease and cancer in particular. Chronic inflammation caused by tobacco smoke plays a significant role in the pathophysiology of chronic diseases. To date, several cytokines have been identified to associate with smoking, but mainly a few inflammatory cytokines have repeatedly been reported. Broader mapping of smoking-related cytokines could help to understand the chronic disease pathogenesis better.

The aim of this study was to elucidate the associations between daily smoking and inflammatory markers such as cytokines, chemokines, and growth factors measured from serum. This study is a part of the ongoing population-based Cardiovascular Risk in Young Finns Study (YFS). The concentrations of 48 cytokines, chemokines, and growth factors were measured with multiplex assay kits. Smoking status was self-reported on a structured questionnaire and a categorized variable was constructed (daily/occasionally/quit/never). Age, BMI, systolic blood pressure, HDL and LDL cholesterol, triglycerides, physical activity level, diet, and alcohol use were used as covariates in the statistical analyses. Analysis of covariance was used to study the differences between the never smoking and other smoking groups. The analyses were performed separately for men and women.

Compared to never smoking, daily smoking associated with six cytokines, including three growth factors (HGF, βNGF and SCF) and three inflammatory cytokines (CXCL10, CXCL9 and IL-18). In men and women, daily smoking was directly associated with HGF (Men: β=0.178, SE=0.038, P<0.001; women: β=0.122, SE=0.036, P<0.001) and indirectly with CXCL10 (Men: β =-0.182, SE=0.050, P<0.001; women: β =-0.245, SE=0.050, P<0.001). In women, daily smoking was indirectly associated with CXCL9 (β=-0.195, SE= 0.055, P<0.001) and with βNGF (β=-0.176, SE= 0.051, P<0.001). Furthermore, in men, daily smoking was indirectly associated with SCF (β=-0.115, SE=0.034, P<0.001) and directly associated with IL-18 (β=0.157, SE=0.039, P<0.001), but these associations diluted after adjusting for the covariates.

My findings support previous studies showing that smoking is associated with acute phase reactions of innate immunity, and with dampening of the adaptive immune response. In addition, I provide novel insight to the study field by showing associations of HGF and βNGF with daily smoking.