The role of lipopolysaccharide in the development of atopy in humans.

Atopy is a highly prevalent condition and remains the single biggest risk factor for asthma. Although atopy has a heritable component, the time frame of the increase in the prevalence indicates that it is not due to genetic factors alone. Lipopolysaccharide (LPS) and its bioactive moiety endotoxin are common to all gram-negative bacteria and can readily measured in dust from homes. Some, but not all, studies have demonstrated an inverse dose–response relationship between exposure to endotoxin and the risk of atopy. It has now been demonstrated in four independent populations that high exposure to endotoxin in the domestic environment is protective against the development of atopy, but only among carriers of the C allele, that is, the environmental exposure is only relevant when taken in the context of the genotype. Furthermore, this interaction is biologically plausible. We propose that neither the environmental exposure nor the genotype in isolation is sufficient to cause complex diseases like asthma and atopy, but disease results from the one acting in the context of the other, of which CD14 and endotoxin is one example contributing to the risk for atopy. Clin Exp Allergy. 2009 Nov 25. [Epub ahead of print]