The role of endotoxin and its receptors in allergic disease.
OBJECTIVE
To summarize the existing literature on the association of endotoxin with respiratory diseases and allergic sensitization and to review the potentially modifying effects of endotoxin receptor polymorphisms.


METHODS
English-language articles were identified from the MEDLINE and PubMed databases using combinations of the following search terms: endotoxin, toll-like receptor, polymorphisms, atopy, asthma, and allergy. Other sources included experts in the field and the bibliographies of pertinent articles.


METHODS
Relevant articles were selected based on the authors' expert opinion.


RESULTS
Cross-sectional studies, particularly those of children raised in rural European communities, suggest that early endotoxin exposure may protect against the development of allergic sensitization and atopic asthma. However, endotoxin exposure may also contribute to other nonatopic respiratory disorders and may exacerbate disease in individuals with preexisting asthma. Paradoxically, among individuals exposed to high levels of endotoxin, carriers of a functional mutation in toll-like receptor 4, which reduces cellular responsiveness to endotoxin, may be at lower risk of developing allergic sensitization.


CONCLUSIONS
The effect of endotoxin exposure on allergic sensitization and asthma appears to be influenced by the timing of exposure, the presence or absence of preexisting disease, and polymorphisms in the genes that encode endotoxin receptors. Further studies are needed to define the window period for this effect, as well as the underlying immunologic mechanism.
Williams
L Keoki
LK
Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan 48202, USA. kwillia5@hfhs.org
Ownby
Dennis R
DR
Maliarik
Mary J
MJ
Johnson
Christine C
CC
D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004731:Endotoxins / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics; D011971:Receptors, Immunologic / Q000276:immunology*; D012140:Respiratory Tract Diseases / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D004731:Endotoxins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C048071:endotoxin receptor