Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: A randomized laboratory study

Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA. Multiple parameters of asthma-like pulmonary inflammation were measured.Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and IgG1 were significantly reduced, however no change in CRA-specific IgE was detected. In HDE mice, plasma IgG2a levels were similar to na？ve mice, while LPS-reduced HDE mice had significantly greater concentrations. Reduced levels of LPS in the HDE did not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine challenge. Conclusion: These data show that reduction of LPS levels in the HDE does not significantly protect against the severity of asthma-like pulmonary inflammation.Asthma is a chronic allergic disorder characterized by IgE production, airway eosinophilia and bronchial hyperresponsiveness[2]. Numerous studies have shown that allergens are not solely responsible for the severity of the asthmatic response (reviewed in[3]). Microbial components, such as lipopolysaccharide (LPS) from Gram negative bacteria, are ubiquitously present in the environment, including the ambient air. In addition to being potent activators of innate immunity, these compounds have been shown to modulate asthma severity[4]. The presence of microbial components often is associated with environmental and household cleanliness, however the hygiene hypothesis postulates that the lack of exposure to these pathog