:  +1-617-803-9415
search
Our Service
Intrabronchial LPS-Induced Acute Lung Injury (ALI) Model

Severe acute lung injury (ALI) in humans, usually associating with infectious etiologies of sepsis or pneumonia, is a significant cause of morbidity and mortality in critically ill patients. 

Acute respiratory LPS challenge models in animals as well as in humans which are characterized by bronchoalveolar neutrophil influx and cytokine up-regulation, have been extensively used for the testing of new anti-inflammatory drugs although they do not reflect all features of human, notably chronic, respiratory diseases.

The close phylogenetic relationship between NHP and humans, and the resulting high homology to a variety of human target structures make NHP interesting for preclinical testing of newly developed drugs.


Case Study: Anti-inflammatory activity of the bradykinin B1R antagonist in a model of LPS-induced lung inflammation in the cynomolgus monkey

image.png

At 12h post LPS challenge, BAL cells were significantly elevated (p < 0.05) over baseline (LPS: 20 x 106 vs naive: 2 x 106) which was mainly due to an accumulation of neutrophils (LPS: 80 % vs naive: 1.5 %). BALF protein was significantly increased (p < 0.05) 12 h after LPS challenge (LPS: 3 mg/ml vs naive: 0.9 mg/ml). Of all the cytokines measured, only BALF IL-8 was significantly increased (p < 0.05) 12 h after LPS challenge (LPS: 1100 pg/ml vs naive: 200 pg/ml). 

The number of neutrophils and other inflammatory parameters returned to baseline level one week after LPS challenge. All treatments, B1R antagonist, PDE4 inhibitor and dexamethasone, significantly reduced (p < 0.05) LPS-induced BAL neutrophilia (~80 % inhibition) and BALF protein (~90 % inhibition). The B1R-antagonist inhibited BALF IL-8 by 50 %, dexamethasone by 80 % and the PDE4 inhibitor by 100%. 

These data show that a cross-over design in the model of LPS-induced lung inflammation in the cynomolgus monkey is meaningful because all inflammatory parameters returned to baseline one week after LPS challenge. In this study the B1R antagonist displayed an anti-inflammatory activity similar to dexamethasone and the PDE4 inhibitor.


Cytokine responses in LPS-induced lung inflammation model:

1582534195134035.png

More data about the LPS-induced lung inflammation model Cytokines in BALF:

1582534235301680.png




Fill out my online form