[Frontiers in Bioscience S5, 754-765, January 1, 2013]

Causes and consequences of low grade endotoxemia and inflammatory diseases

Trevor G. Glaros1, Samantha Chang1, Elizabeth A. Gilliam1, Urmila Maitra1, Hui Deng1, Liwu Li1

1Laboratory of Innate Immunity and Inflammation, Department of Biological Science,Virginia Polytechnic Institute and State University, Blacksburg, VA 24060

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Causes of low dose endotoxemia
3.1 .Chronic consumption of alcohol
3.2 .Chronic smoking
3.3 .Obesity and high fat diet
3.4 .Periodontal disease
3.5 .Aging
4. Pathological consequences of low dose endotoxemia
4.1 .Diabetes and insulin resistance
4.2 .Inflammation and obesity
4.3 .Atherosclerosis
4.4 .Parkinson's disease
5. Molecular mechanisms responsible for the pro-inflammatory skewing of innate immune environment by low dose LPS
6. Summary and perspective
7. Acknowledgements
8. References

1. ABSTRACT

Increasing clinical observations reveal that persistent low-grade inflammation is associated with the pathogenesis of severe chronic diseases such as atherosclerosis, diabetes, and aging-related neurological diseases. Intriguingly, low levels of circulating Gram-negative bacterial endotoxin lipopolysaccharide (LPS) appear to be one of the key culprits in provoking a non-resolving low-grade inflammation. Adverse life styles, chronic infection, and aging can all contribute to the rise of circulating endotoxin levels and lead to low-grade endotoxemia. As a consequence, low-grade endotoxemia may skew host immune environment into a mild non-resolving pro-inflammatory state, which eventually leads to the pathogenesis and progression of inflammatory diseases. This review aims to highlight the recent progress in the causes and consequences of low-grade endotoxemia, as well as the emerging molecular mechanisms responsible.