Particulate Matter Induces Translocation of IL-6 from the Lung to the Systemic Circulation

Abstract

The biological mechanisms responsible for an association between elevated concentrations of ambient particulate matter (PM) and increased cardiovascular morbidity and mortality remain unclear. Our laboratory showed that exposure to PM induces systemic inflammation that contributes to vascular dysfunction. This study was designed to determine whether the lung is a major source of systemic inflammatory mediators, using IL-6 as a surrogate marker. We also sought to determine the impact on vascular dysfunction after exposure to PM of less than 10 μm in diameter (PM(10)). C57BL/6 mice were intratracheally exposed to a single instillation of PM(10) (10 or 200 μg) or saline. Four hours or 24 hours after exposure, venous and arterial blood samples were simultaneously collected from the right atrium and descending aorta. Concentrations of IL-6 were measured in bronchoalveolar lavage fluid (BALF) and serum samples. Vascular functional responses to acetylcholine (ACh) and phenylephrine were measured in the abdominal aorta. Concentrations of IL-6 in BALF samples were increased at 4 and 24 hours after exposure to PM(10). At baseline, concentrations of IL-6 in venous blood were higher than those in arterial blood. Exposure to PM(10) reversed this arteriovenous gradient, 4 hours after exposure. The relaxation responses of the abdominal aorta to ACh decreased 4 hours after exposure to 200 μg PM(10). In IL-6 knockout mice, the instillation of recombinant IL-6 increased IL-6 concentrations in the blood, and exposure to PM(10) did not cause vascular dysfunction. These results support our hypothesis that exposure to PM(10) increases pulmonary inflammatory mediators that translocate to the circulation, contributing to systemic inflammation, with downstream effects such as vascular dysfunction.

The possible protective role of quercetin on induced cardiac Oxidative DNA Damage by repeated exposure to diesel exhaust nanoparticles in rats (a histological and immunohistochemical study)

“…Similar results were seen after a single dose and repeated dose administration of particles [8,[26][27][28]. Studies by Nemmar et al [26] in humans showed doi: 10.7243/2055-091X-5-2 an increase in a number of mast cells and neutrophils in the bronchial submucosa along with an increase in myeloperoxidase and interleukin 8 (IL-8) concentrations.…”

Air Pollution and Cardiovascular Disease

“…The generation of a systemic inflammatory response, mostly demonstrated by increases in C-reactive protein (CRP) (Peters et al 2001b, Hertel et al 2010, is of major importance in the pathogenesis of cardiovascular events. Upon PM exposure, IL-6 translocates from the lung into the systemic circulation (Kido et al 2011) and is directly involved in the regulation of the synthesis of CRP in the liver. Elevated concentrations of IL-6 are associated with an increased risk of cardiovascular events (Ridker et al 2000, Lindmark et al 2001) and mortality (Volpato et al 2001).…”

Influence of the Chronic Obstructive Pulmonary Disease on Post-Operation Course in Coronary Heart Disease

“…При этом запускаются процессы окисления липидов и липопротеидов, что ведет к накоплению холесте-рина, а также увеличивает в токе крови количество цитокинов, белков острой фазы, лейкоцитов и тром-боцитов. Данные биохимические нарушения, в свою очередь, способствуют усилению эндотелиальной дис-функции [8]. Итогом такого комплексного воздей-ствия является снижение коронарного резерва, что ведет к прогрессированию проявления ИБС и разви-тию мультифокального поражения артериального русла [9].…”