Using segmental LPS challenge to demonstrate the effectiveness of a B1R antagonist

Drugs that specifically target signaling pathways in inflammatory diseases could help to treat patients with chronic obstructive pulmonary disease (COPD). Bradykinin receptor-1 (B1R) is activated during inflammation and increases the migration of pro-inflammatory cells to the lungs. The company Boehringer Ingelheim has developed an antagonist that can block B1R and thus has the potential to reduce inflammation of the lungs. At Fraunhofer ITEM, the segmental lipopolysaccharide (LPS) challenge model was used to test the safety, tolerability and effectiveness of the B1R antagonist. Segmental challenge involves instilling LPS, a component of the bacterial cell wall, into the lungs, where it causes a local inflammatory reaction. Over a period of four weeks, the B1R antagonist was administered to 29 healthy subjects, and placebo was given to 28 healthy subjects. Both treatments were administered orally twice daily.

By determining the number of neutrophils in the bronchoalveolar lavage following LPS challenge, researchers examined whether the inflammatory response was reduced in the B1R antagonist treated group compared to the placebo group. Treatment with the B1R antagonist was found to be safe and well tolerated. However, it did not lead to a reduction in the number of neutrophils in the LPS challenge model. The results were published in the Pulmonary Pharmacology & Therapeutics journal (Gress, C. et al., 2023: DOI 10.1016/j.pupt.2023.102246).