HYGIENE  ENDOTOXIN  EARLY INTERVENTION  CHILDHOOD ASTHMA  INNER CITY ASTHMA  RHINOSINUSITIS  NATURAL HISTORY Andrew H. Liu, M.D. Staff Contact in association with:

click to enlarge We have found it helpful to study bacterial endotoxin as a prototypical microbial adjuvant and exposure that may alter atopy, allergy, and asthma outcomes. Endotoxin Background: Endotoxin makes up most of the outer cell wall of all gram-negative bacteria, and is the natural ligand for TLR 4. In stimulating innate immune cells, Endotoxin is a potent inducer of immune memory, of Th1 immune development, and also of regulatory immune mechanisms that keep immune responses appropriately contained and controlled. Endotoxin is therefore considered to be a prototypical PAMP, or Pathogen-Associated Molecular Pattern, which are fundamental components of microbes that the immune system relies heavily on to recognize them. click to enlarge Endotoxin exposure may be both harmful and helpful: Harmful in that, at high exposure levels, some can develop endotoxin-sensitive asthma, such as occupational forms of asthma like byssinosis. If asthma or allergic diseases are ongoing, then endotoxin is like gas on a flame and will increase inflammation and severity. Helpful in that endotoxin could downmodulate atopy and promote healthful immune responses to microbial pathogens and other environmental exposures such as allergens Most importantly, the determinants for harmful or healthful outcomes include: timing, dosage, environmental co-factors, and genetics. LiuLab publications Reviews: Liu JACI 2002: Comprehensive review on endotoxin exposure and atopy, allergy and asthma outcomes Liu/Murphy JACI 2003: Weighing the clinical evidence on the hygiene hypothesis Song/Liu CurrOpin 2003: Annotated update of endotoxin exposure in metropolitan communities and allergy and asthma outcomes Liu J Respir Dis 2004: Editorial with pro-con debate on the hygiene hypothesis Articles: Gereda/Liu Lancet 2000: Original article on less dust endotoxin and blood Th1-type cells in atopic infants Gereda/Liu JAMA 2000: Original article on more dust endotoxin in U.S. farm homes and barns, and rural homes from India and Peru Gereda/Liu JACI 2000: Original article on more endotoxin with furred animals in home, especially dogs and cats Related Hygiene Hypothesis - Nature's Immunotherapy for allergies & asthma? Early Intervention for allergies & asthma Natural history of allergies & asthma in childhood Coming More LiuLab articles on how endotoxin may improve immune responses