Inhaled endotoxin induces a systemic neutrophil response without affecting cardiovascular measures in a randomized cross-over exposure study

Abstract

Objective

The gram-negative bacterial cell wall component endotoxin (lipopolysaccharide, LPS) is a key component of particulate matter (PM). PM exposure is associated with cardiovascular morbidity and mortality. However, the contribution of individual components of PM to acute and chronic cardiovascular measures is not clear. This study examines whether systemic inflammation induced by LPS inhalation causes acute changes in cardiovascular physiology measures.

Materials and Methods

In this double blinded, placebo-controlled crossover study, fifteen adult volunteers underwent inhalation exposure to 20,000 EU Clinical Center Reference Endotoxin (CCRE). Peripheral blood and induced sputum neutrophils were obtained at baseline and six hours post-exposure. Blood pressure, measures of left ventricular function (ejection fraction (LVEF) and global longitudinal strain (LVGLS)), and indices of endothelial function (flow mediated dilation (FMD) and velocity time integral during hyperemia (VTIhyp)) were measured before and after treatment. Wilcoxon sign-rank tests and linear mixed models were used for statistical analysis.

Results

In comparison with normal saline, LPS inhalation resulted in significant increases in peripheral blood and sputum neutrophils but was not associated with significant alterations in blood pressure, LVGLS, LVEF, FMD, or VTIhyp.

Discussion and Conclusions

In healthy adults, systemic inflammation after LPS inhalation was not associated with acute changes in cardiovascular physiology. Larger studies are needed to investigate the effects of other PM components on inflammation induced cardiovascular dysfunction.

Keywords:

• Endotoxin
• lipopolysaccharide (LPS); pollution
• particulate matter
• cardiovascular physiology effects

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Additional information

Funding

This work was supported National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institute of Environmental Health SciencesResearch reported in this publication was supported by the Assistance Agreement No. 83578501-0 awarded by the U.S. Environmental Protection Agency to the University of North Carolina, NIAID T32AI007062 (SAS), NHLBI T32HL007106 (SAS), KL2TR002490 (AJB), and 1K12TR004416 (SAS and AJB). Haolin Li is supported by the NIEHS training grant T32ES007018, and Haibo Zhou is supported in part by grants P42ES031007 and P30ES010126. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or EPA. Clinicaltrials.gov: NCT03623022