Systemic and local airways inflammatory response to endotoxin

doi:10.1016/S0300-483X(00)00288-2

Toxicology

Volume 152, Issues 1–3, 2 November 2000, Pages 25-30

https://doi.org/10.1016/S0300-483X(00)00288-2 Get rights and content

Abstract

Endotoxin can be detected in house dust. Numerous studies have revealed that endotoxin exposure is a risk factor in increasing airway obstructive manifestations, both in occupational and domestic environments. In humans, inhalation of pure endotoxin induces systemic symptoms and a change in bronchial non-specific responsiveness, related with changes in blood and sputum inflammatory markers. However, some recent work suggests that, prior to airway disease development, endotoxin may have an atopy-protective effect. In particular, indoor endotoxin exposure in early life may protect against allergen sensitisation by enhancing type-1 immunity. Finally, since large variations between human immune responses to endotoxin have been reported, genetic mutations could alter the mechanisms of endotoxin recognition and contribute to the risk of atopy.

Introduction

Endotoxin and its purified derivative lipopolysaccharide (LPS) are Gram-negative bacterial constituents present in the oral and nasal cavities and also in the environment. Aspiration of secretions from the mouth and nasopharynx may lead to bronchial contamination by endotoxins, since Gram-negative bacteria are frequently present in the normal pharynx (Rosenthal and Tager, 1975). Endotoxins are found in commercial milk samples, that could reach the lung by gastroesophageal reflux or by inhalation (Di Luzio and Friedman, 1973) and in domestic water, that could be inhaled in bathrooms (Muittari et al., 1980). Hasday et al. (1999) reported that high levels of bacterial endotoxin are produced by cigarette smoke. Airborne endotoxins have been detected in several occupational environments, such as agricultural environments (grain, swine confinement, poultry farm), industrial environments (cotton mill, potato processing, brewery, fiberglass industry) and waste processing (Milton et al., 1995; Jacobs, 1997). In the domestic environment, there is also endotoxin contaminating house dust (Michel et al., 1996; Rizzo et al., 1997).

Endotoxin is an extremely potent toxin: macrophages can be activated at concentrations of LPS as low as 1 ng/ml leading to the synthesis and release of proinflammatory cytokines, arachidonic acid metabolites and various other mediators (Ingalls et al., 1999). Endotoxin, being a contaminant of house dust, could be a pathogenic factor in asthma, worsening the bronchial inflammation, the degree of bronchial hyperreactivity (BHR) and the clinical status. This paper reviews the human response to inhalation of pure endotoxin.

Section snippets

Clinical and lung function response

Inhalation of ≥30 μg of pure endotoxin may elicit symptoms in some individuals. Short periods (4–12 h) of dyspnea, chest tightness, myalgia, shivers, fatigue and malaise have been reported, associated or not with fever (Rylander et al., 1989; Michel et al., 1997). A similar clinical response is observed in workers (and in some normal subjects) after exposure to dust containing endotoxin, such as grain handlers (Jagielo et al., 1996), cotton workers (Rylander et al., 1985), fiber glass

Inflammatory response

Local and systemic inflammatory responses have been measured after endotoxin inhalation in normal and asthmatic subjects. Significant blood leukocytosis and neutrophilia were observed 4–8 h after >20 μg inhaled endotoxin both in normal (Herbert et al., 1992; Michel et al., 1995; Michel et al., 1997) and asthmatic subjects (Michel et al., 1992a). This endotoxin-induced neutrophilia was not related to the change in lung function (Van der Zwan et al., 1982; Michel et al., 1995; Michel et al., 1997

Subject-dependent responsiveness to endotoxin

The sensitivity to endotoxin varies considerably among animal species, humans being very sensitive. In normal subjects, endotoxin inhalation induces dose-related clinical symptoms, changes in lung function and both a bronchial and systemic inflammatory response (Michel et al., 1997). However, there is a considerable inter-individual variability in the amplitude of both the clinical and inflammatory responses to endotoxin by inhalation (Van der Zwan et al., 1982; Castellan et al., 1987; Michel

Synergic effect with allergens

There is some published data suggesting that environmental endotoxin could be a synergic factor on the amplitude of IgE-mediated response.

On one side, in an allergic mild asthmatic, an exposure to air containing low level of endotoxin (250 ng/m³) for 4 h before bronchial challenge with allergen, increases significantly both bronchial reactivity and antigen-induced airway eosinophilia (Boehlecke et al., 1999). The cellular inflammation to allergen inhaled into the airways is modified by

Conclusions

Endotoxin are pro-inflammatory agents, present in occupational and domestic environments. These Gram-negative bacteria constituents are also present in the gut and the oral and nasal cavities of humans. By interacting with the host, endotoxin activates the innate immune system that provides instructions for maturation of the acquired immunity. On the other side, endotoxin induces a local and systemic inflammatory response in normal subjects that could contribute to the risk of developing asthma

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Systemic and local airways inflammatory response to endotoxin

Abstract

Introduction

Section snippets

Clinical and lung function response

Inflammatory response

Subject-dependent responsiveness to endotoxin

Synergic effect with allergens

Conclusions

Chest

Chest

Infect. Dis. Clin. North Am.

Chest

Lancet

A polymorphism in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum Immunoglobulin E

Am. J. Respir. Cell. Mol. Biol.

Exposure to low level of endotoxin for four hours increased response to inhaled mite allergen in mild asthmatics

Am. J. Respir. Crit. Care Med.

Inhaled endotoxin and decreased spirometric values

New Engl. J. Med.

Effects in man and rabbits of inhalation of cotton dusts or extracts and purified endotoxin

Br. J. Ind. Med.

Grain dust-induced airflow obstruction and inflammation of the lower respiratory tract

Am. J. Respir. Crit. Care Med.

Bacterial endotoxin in the environment

Nature

Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment

Am. J. Physiol.

Endotoxin-induced inflammation and injury of the guinea pig respiratory airways cause bronchial hyporeactivity

Am. Rev. Respir. Dis.

Lipopolysaccharide and cytokines: a tangled web

Endotoxin contamination causes neutrophilia following pulmonary allergen challenge

Am. J. Respir. Crit. Care Med.

Endotoxins in the environment: a criteria document

Int. J. Occup. Environ. Health

Variable airway responsiveness to inhaled lipopolysaccharide

Am. J. Respir. Crit. Care Med.

Swine dust causes intense airways inflammation in healthy subjects

Am. J. Respir. Crit. Care Med.

Lipopolysaccharide binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide

J. Clin. Invest.

Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome

Am. J. Respir. Crit. Care Med.

Effect of inhaled endotoxin on bronchial reactivity in asthmatic and normal subjects

J. Appl. Physiol.