Innate Immun. 2017 Apr;23(3):249-257. doi: 10.1177/1753425917690443.

Dose-dependent immunomodulating effects of endotoxin in allergic airway inflammation.

Sudhir Kumar1,2, Atin Adhikari3.
1 Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
2 Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA.
3 Department of Epidemiology & Environmental Health Sciences, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA.




Bacterial endotoxin or lipopolysaccharide (LPS) is present everywhere in environments with different concentrations. It can influence airway immunomodulation and asthma aggravations. However, exposure levels and duration of exposures are key determinants of its immunomodulatory properties. The risks associated with endotoxin induced atopic asthma are less in children grown in farms or rural environments in comparison to urban environments. Several studies have pointed out that innate as well as adaptive immune responses differ with different extent of endotoxin exposures.

The principle innate immune component, such as Toll like receptors (TLRs), recognizes a wide range of microbial products and is associated with initiation of both innate and adaptive immune responses. Inflammatory responses such as Th1 and Th2 polarization are also influenced by LPS exposures. Further, immune homeostasis, such as T regulatory cells (Tregs), can maintain immunological properties of endotoxin when mice were treated with different doses. In this study, we have observed that low doses of endotoxin exposure are associated with elevation of allergic airway immune responses along with the higher production of eosinophils and serum IgE, whereas high dose of endotoxin exposure to mice develops immune tolerance by induction of Tregs.

In addition, cytokine signature in different doses of endotoxin exposed mice suggests that low dose of LPS favors higher levels of Th2 cytokine production in contrast to high dose. Our observations also indicate that inappropriate generation of LPS-induced antigen specific immune responses at low dose may suppress the antigen specific immune regulatory network. Additionally, low production of IFN-γ at low dose of endotoxin exposure interrupts development of airway allergic tolerance, whereas high dose of LPS is associated with inhibition of airway allergic response through generation of antigen specific immune responses. Taken together, the findings presented in this article showed importance of different doses of LPS in establishing ongoing allergen-induced immune homeostasis network. These finding could be useful in explaining unusual associations between endotoxin exposures and atopic asthma in farming environment versus urban environment.