Serum IL8 is not associated with cardiovascular events but with all-cause mortality.

BACKGROUND: The aim of this study is to investigate if IL8 levels were associated with incident cardiovascular (CV) events (CVE) and mortality (all-cause, CV, and cancer) in a cohort of 60 years old men and women from Stockholm (60YO). METHODS: The 60YO comprises 4232 participants; baseline period: 1997-1999. The cohort is matched annually to population registries to record deaths and incident CVE. Serum IL8 was measured in 4011 participants and categorized in quartiles. Cox proportional hazard models were used to estimate the CVE and mortality risk, expressed as hazard ratios (HR) with 95% confidence intervals (CI). Potential confounding was addressed by adjusting for traditional CV risk factors (CVE estimates) and by sex, life style habits, metabolic factors (mortality estimates). Laplace regression was used to calculate the difference in time until a certain percentage of the cohort died according to IL8 levels. RESULTS: During 16.5 years follow up, 522 incident CVE were recorded and 647 study participants died. IL8 was not associated with CVE risk (IL8 Q4 vs Q1, HR of 0.95; 95% CI 0.75-1.22). Compared to Q1, IL8 Q4 was associated with all-cause mortality (adjusted HR 1.28; 95% CI 1.02-1.63). No association was observed with CV and cancer related mortality in the fully adjusted model. Participants with IL8 above the median died of any cause ≈1.3 years before the 15% of the population had died. CONCLUSION: Elevated IL8 levels were not associated with CVE risk and CV mortality, but were associated with an increased risk of all-cause mortality regardless of the underlying cause.

Interleukin 6 trans-signalling and risk of future cardiovascular events.

Aims: The pro-inflammatory response to interleukin 6 (IL6) trans-signalling in atherosclerosis is driven by the IL6 and soluble IL6 receptor (sIL6R) binary complex. The binary IL6:sIL6R complex is inactivated by sgp130 through the formation of the ternary IL6:sIL6R:sgp130 complex. The aim of this study was to investigate if IL6 trans-signalling, estimated by a ratio between the binary and ternary complexes, associates with the risk of future cardiovascular events (CVE) in a Swedish cohort of 60-year-old men and women (n = 4232). Methods and results: Binary and ternary complex levels expressed in nanomol/Litre were derived from serum concentrations of IL6, sIL6R, and sgp130. Cox regression models were used to assess the risk of CVE (myocardial infarction, angina pectoris, and ischaemic stroke, n = 525), expressed as hazard ratio (HR) with 95% confidence interval (CI), associated with increasing circulating levels of the three molecules and with the binary/ternary complex ratio. Estimates were adjusted for the common cardiovascular (CV) risk factors. To assess the level of IL6-trans-signalling, we estimated the binary/ternary complex ratio and then analysed the association with CVE risk. A ratio higher than the median, representing a relative excess of the active binary complex was associated with increased CVE risk (adjusted HR 1.44, 95% CI 1.21-1.72). Conclusion: The ratio between the functional moieties of IL6 trans-signalling, IL6:sIL6R, and IL6:sIL6R:sgp130, was associated with CVE risk indicating that it could be a promising marker of CV risk and possibly be used in selecting patients for anti-inflammatory therapy.

Exposure to Traffic-Related Air Pollution and Serum Inflammatory Cytokines in Children.

BACKGROUND: Long-term exposure to ambient air pollution can lead to adverse health effects in children; however, underlying biological mechanisms are not fully understood. OBJECTIVES: We evaluated the effect of air pollution exposure during different time periods on mRNA expression as well as circulating levels of inflammatory cytokines in children. METHODS: We measured a panel of 10 inflammatory markers in peripheral blood samples from 670 8-y-old children in the Barn/Child, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) birth cohort. Outdoor concentrations of nitrogen dioxide (NO2) and particulate matter (PM) with aerodynamic diameter <10 µm (PM10) from road traffic were estimated for residential, daycare, and school addresses using dispersion modeling. Time-weighted average exposures during infancy and at biosampling were linked to serum cytokine levels using linear regression analysis. Furthermore, gene expression data from 16-year-olds in BAMSE (n=238) were used to evaluate links between air pollution exposure and expression of genes coding for the studied inflammatory markers. RESULTS: A 10 µg/m3 increase of NO2 exposure during infancy was associated with a 13.6% (95% confidence interval (CI): 0.8; 28.1%) increase in interleukin-6 (IL-6) levels, as well as with a 27.8% (95% CI: 4.6, 56.2%) increase in IL-10 levels, the latter limited to children with asthma. However, no clear associations were observed for current exposure. Results were similar using PM10, which showed a high correlation with NO2. The functional analysis identified several differentially expressed genes in response to air pollution exposure during infancy, including IL10, IL13, and TNF;. CONCLUSION: Our results indicate alterations in systemic inflammatory markers in 8-y-old children in relation to early-life exposure to traffic-related air pollution. https://doi.org/10.1289/EHP460.