Bradykinin

Where it comes from

Made in

Cut from high-molecular-weight kininogen in blood by plasma kallikrein, when the contact system fires

Sent out by

Tissue injury, inflammation, contact with foreign surfaces, and uncontrolled kallikrein in hereditary angioedema

Acts on

• Endothelium (nitric oxide, prostacyclin, leak)
• Pain nerves
• Smooth muscle of airway and gut

What it does

• Widens vessels and makes them leak, so tissue swells
• Fires pain nerves directly
• Contracts the airways and the gut
• Destroyed in seconds by ACE, which is why ACE inhibitors cause cough and, rarely, angioedema

In medicine

• Hereditary angioedema is bradykinin disease: icatibant blocks its B2 receptor during an attack ¹; ecallantide, lanadelumab, berotralstat and sebetralstat stop the kallikrein that makes it ²; garadacimab stops factor XII above that
• Measuring it is not practical; its half-life is under 30 seconds

Beyond the body’s own use

• Bradykinin was suspected in the leaky lungs of severe COVID-19. A randomised open-label trial of icatibant in 73 inpatients with COVID-19 pneumonia did not meet its primary outcome, a clinical response by day 10 ³
• Lobradimil, a bradykinin B2 agonist, was given to open the blood-brain barrier for chemotherapy. In a paediatric phase 2 trial the combination was inactive in high-grade and brainstem glioma, and the approach was dropped ⁴
• Nothing is taken outside medicine, and nothing could be. Bradykinin lasts under thirty seconds in blood, and what people in fact need in angioedema are the blockers, every one of which is a prescription medicine ¹