Endotoxin Exposure - What It Is and What It Does To Your Health!  Free

EndoToxins and Your Health 

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Endotoxin exposure appears to be an important cause of environmental airway disease. Workers in intensive livestock and agricultural operations such as cotton production, swine confinement facilities, poultry production plants, and grain dust operations are exposed to high concentrations of endotoxin and develop acute decrements in airflow as a result of their occupations.

In studies supported by NIEHS, researchers have shown that endotoxin in the bioaerosol is the most important occupational exposure associated with the development and progression of airway disease in agricultural workers. Exposures to grain dust that contains endotoxin can cause airflow obstruction in previously unexposed individuals and this obstruction can result within 30 minutes of exposure. This response is dependent on the dose of grain dust inhaled. Dr. David Schwartz (R01ES06537), Professor of Internal Medicine, Director of the Center for Environmental Lung Diseases and member of the NIEHS Environmental Health Sciences Center at the University of Iowa, has lead a team of researchers on an investigation that includes epidemiologic studies of risk factors for environmental airway disease in agricultural workers, and genetic research searching for the LPS gene which may be responsible for regulating the host's susceptibility to environmental endotoxin.

Epidemiologic studies have shown that the concentration of endotoxin in the bioaerosol is strongly associated with respiratory systems, airflow obstruction and longitudinal declines in airflow among grain handlers. Acute declines in lung function were also found across the work shift and higher concentrations in endotoxin was associated with a steeper rate of decline. These findings prompted Dr. Schwartz's team to develop animal and human exposure-response models that would allow for continued investigation of the mechanism of these effects.

In humans, Dr. Schwartz found that the physiological and inflammatory responses to inhaled grain dust are similar to those observed following lipopolysaccharide (LPS) exposure. Following inhalation of either agent, healthy nonasthmatic, nonatopic subjects without previous airway hyperreactivity develop significant declines in airflow; FEV1 declines 10-40%. These symptoms are associated with a neutrophilic alveolitis, activated macrophages that produce and release specific proinflammatory cytokines and airway epithelia that produce and release IL-8. Kinetic studies showed that this occurs within 10 minutes of exposure and persists for 48 hours. Modifying the concentration of endotoxin in grain dust substantially reduces these inflammatory responses. Responsiveness to endotoxin is critical to the development of grain-dust inflammation in the lower respiratory tract. In a mouse model that is resistant to endotoxin effects, these pulmonary effects are not seen. These findings prompted Dr. Schwartz to investigate the role of susceptibility to LPS as an important mechanism to understanding its pulmonary consequences.

Dr. Schwartz and colleagues are conducting research to identify and characterize the LPS gene in mice. Their results have shown that the LPS gene is a single gene with classical Mendelian genetics and does not overlap with the type I interferon genes (IFN-a or IFN-b), as previously believed. These have reduced the critical region of the LPS gene to a discrete (0.5 cM) region in chromosome 4 and have identified some novel genetic markers linked to the LPS gene, and have made progress in constructing a contig across the LPS critical region.

Through NIEHS support. Dr. Schwartz and his colleagues (Merchant; P30ES05605) have significantly advanced our knowledge of the effects of endotoxin in the development of airway disease in populations of agricultural workers. This can be extended to study other agricultural and livestock workers where the potential for exposure to endotoxin is high. Environmental sources of endotoxin in communities surrounding these intensive livestock and agricultural production facilities may also be a significant risk factor for respiratory diseases. There is evidence by others that endotoxin exposure may also cause asthma. Work by Schwartz and others on the identification of an endotoxin susceptibility gene may open possibilities for the future identification of subgroups of the population that are more susceptible to the effects of these exposures. By reducing exposure to these groups, environmental airway disease may be prevented.