Impaired lipopolysaccharide responsiveness of cord blood mononuclear cells and the risk of asthma: A longitudinal study

Background: We previously demonstrated that the proliferative response to lipopolysaccharide (LPS) in cord blood mononuclear cells (CBMCs) is negatively correlated with the induced expression of interleukin (IL)-4. Our aim, therefore, was to examine whether an impaired cellular response to LPS in infancy is associated with the risk for asthma.Methods: In a prospective cohort study, the relationship between the CBMC response to LPS and the risk of atopy and wheezing after the age of 4 y was evaluated.Results: LPS-induced CBMC proliferative responses varied markedly among the 102 infants studied (range, one-to fivefold increase over cells with diluent alone). Ninety-five infants (93%) were followed longitudinally. A higher CBMC proliferative response to LPS was noted in offspring born to nonatopic parents compared with those with at least one atopic parent (P = 0.008). Using a proliferative index cutoff of 2 separated patients into high and low induced IL-4 mRNA responders (P = 0.001). Significantly more children who never wheezed had a greater than twofold LPS-induced CBMC proliferative response compared to those with persistent atopic wheezing (P = 0.046).Conclusion: These results demonstrate that CBMC proliferative responses to LPS is impaired in infants born to atopic parents and may be a risk factor for asthma later in life.