Differences in arterial and mixed venous IL-6 levels: The lungs as a source of cytokine storm in sepsis

Tyburski, James G.; Dente, Christopher J.; Wilson, Robert F.; Steffes, Christopher P.; Devlin, John W.; Carlin, Arthur M.; Flynn, Lisa; Shanti, Christina

doi:10.1067/msy.2001.118094

Cited by 21 publications

(16 citation statements)

References 7 publications

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“…Therefore, the contribution of IL-6 from other sources is likely to be very small (28). Tyburski and colleagues also showed that the A-V gradient of IL-6 was significantly increased in acute lung disorders such as pneumonia, and was nearly zero in patients without any overt lung disease (38). Our study shows that a relatively mild stimulus for lung inflammation with exposure to PM 10 reverses the A-V gradient, supporting our speculation that exposure to PM 10 causes a translocation of IL-6 from the lung to the systemic circulation.…”

Section: Discussionmentioning

confidence: 92%

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

Kido¹,

Tamagawa²,

Bai³

et al. 2011

Am J Respir Cell Mol Biol

118

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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.

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Section: Discussionmentioning

confidence: 92%

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

Kido¹,

Tamagawa²,

Bai³

et al. 2011

Am J Respir Cell Mol Biol

118

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“…Previous studies have demonstrated IL-6 to be a good predictor of mortality in sepsis, and have shown marked upregulation of the cytokine in lungs of septic patients [7,21]. In vitro studies measuring the direct effects of IL-6 on endothelial permeability have led to varying results depending on the origin of endothelial cells.…”

Section: Discussionmentioning

confidence: 97%

“…TNF-␣ and IL-1␤ are present in high concentrations in bronchoalveolar lavage fluid of patients with sustained ARDS [6], and IL-6 has been shown to be up-regulated in the lungs of septic patients [7]. Studies have shown that TNF-␣ and IL-1␤ can directly alter vascular tone [8] and increase microvascular permeability in endothelial monolayers [9 -11].…”

Section: Introductionmentioning

confidence: 99%

TNF-α and IL-1β Increase Pericyte/Endothelial Cell Co-Culture Permeability

Kerkar¹,

Williams²,

Blocksom³

et al. 2006

Journal of Surgical Research

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“…24,25 IL-1 and TNF-A have been shown to be present in high concentrations in bronchoalveolar lavage fluid of patients with sustained ARDS, and IL-6 has been shown to be upregulated in the lungs of septic patients. 25,26 In a study analyzing cytokines in exhaled breath condensate, increased levels of IL-1, IL-6, and TNF-A were found in patients with inflammatory lung diseases. 27 Pericyte secretion of these cytokines may help regulate inflammatory lung diseases.…”

Section: Discussionmentioning

confidence: 99%