Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children
Charlotte Braun-Fahrländer, M.D., Josef Riedler, M.D., Udo Herz, Ph.D., Waltraud Eder, M.D., Marco Waser, M.Sc., Leticia Grize, Ph.D., Soyoun Maisch, M.D., David Carr, B.Sc., Florian Gerlach, Albrecht Bufe, M.D., Ph.D., Roger P. Lauener, M.D., Rudolf Schierl, Ph.D., Harald Renz, M.D., Dennis Nowak, M.D., Erika von Mutius, M.D., for the Allergy and Endotoxin Study Team
Background In early life, the innate immune system can recognizeboth viable and nonviable parts of microorganisms. Immune activationmay direct the immune response, thus conferring tolerance toallergens such as animal dander or tree and grass pollen.
Methods Parents of children who were 6 to 13 years of age andwere living in rural areas of Germany, Austria, or Switzerlandwhere there were both farming and nonfarming households completeda standardized questionnaire on asthma and hay fever. Bloodsamples were obtained from the children and tested for atopicsensitization; peripheral-blood leukocytes were also harvestedfrom the samples for testing. The levels of endotoxin in thebedding used by these children were examined in relation toclinical findings and to the cytokine-production profiles ofperipheral-blood leukocytes that had been stimulated with lipopolysaccharideand staphylococcal enterotoxin B. Complete data were availablefor 812 children.
Results Endotoxin levels in samples of dust from the child'smattress were inversely related to the occurrence of hay fever,atopic asthma, and atopic sensitization. Nonatopic wheeze wasnot significantly associated with the endotoxin level. Cytokineproduction by leukocytes (production of tumor necrosis factor, interferon-, interleukin-10, and interleukin-12) was inverselyrelated to the endotoxin level in the bedding, indicating amarked down-regulation of immune responses in exposed children.
Conclusions A subject's environmental exposure to endotoxinmay have a crucial role in the development of tolerance to ubiquitousallergens found in natural environments.
Source Information
From the Institute of Social and Preventive Medicine, Basel, Switzerland (C.B.-F., M.W., L.G.); Children's Hospital Salzburg, Salzburg, Austria (J.R., W.E.); the Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps University, Marburg, Germany (U.H., H.R.); the Dr. von Hauner Children's Hospital, Munich, Germany (S.M., D.C., F.G., E.M.); the Department of Experimental Pneumology, Ruhr University, Bochum, Germany (A.B.); University Children's Hospital, Zurich, Switzerland (R.P.L.); and the Institute of Occupational and Environmental Medicine, University of Munich, Munich, Germany (R.S., D.N.).
Address reprint requests to Dr. Braun-Fahrländer at the Institute of Social and Preventive Medicine, University of Basel, Steinengraben 49, CH-4051 Basel, Switzerland, or at c.braun{at}unibas.ch.
Endotoxin and Asthma
Maziak W., Perzanowski M. S., Platts-Mills T. A.E., Speiser D. E., Zippelius A., Braun-Fahrländer C., Lauener R. P., von Mutius E., Weiss S. T.
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N Engl J Med 2003;
348:171-174, Jan 9, 2003.
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