TY - JOUR
T1 - The role of endotoxin and its receptors in allergic disease
AU - Williams, L. Keoki
AU - Ownby, Dennis R.
AU - Maliarik, Mary J.
AU - Johnson, Christine C.
N1 - Funding Information:
* Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan. † Center for Health Services Research, Henry Ford Health System, Detroit, Michigan. ‡ Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan. § Section of Allergy and Immunology, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia. This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases (R01AI61774, R01AI50681) and the Fund for Henry Ford Hospital. Received for publication July 13, 2004. Accepted for publication in revised form October 3, 2004.
PY - 2005/3/1
Y1 - 2005/3/1
N2 - 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. Data Sources: 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. Study Selection: 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.
AB - 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. Data Sources: 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. Study Selection: 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.
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U2 - 10.1016/S1081-1206(10)60983-0
DO - 10.1016/S1081-1206(10)60983-0
M3 - Review article
C2 - 15801242
AN - SCOPUS:15444374455
SN - 1081-1206
VL - 94
SP - 323
EP - 332
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 3
ER -