We investigated the effect of VGX-1027, a TLR4 blocker, on PM<sub>2.5</sub>-induced airway inflammation and bronchial hyperresponsiveness (BHR) in a murine model in vivo and on inflammatory mechanisms in vitro in human airway epithelial cells.
Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94).
Finally, inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma, including bronchial hyperreactivity.
Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/I399 polymorphism in the TLR4 gene.