Effects of the Humanized Anti-Adrenomedullin Antibody Adrecizumab (HAM8101) on Vascular Barrier Function and Survival in Rodent Models of Systemic Inflammation and Sepsis

Shock. 2018 Dec;50(6):648-654. doi: 10.1097/SHK.0000000000001102.


Purpose: Adrenomedullin (ADM) is an important regulator of endothelial barrier function during sepsis. Administration of a murine antibody targeted against the N-terminus of ADM (HAM1101) resulted in improved outcome in models of murine sepsis. We studied the effects of a humanized form of this antibody (HAM8101, also known as Adrecizumab) on vascular barrier dysfunction and survival in rodent models of systemic inflammation and sepsis.

Methods: Rats (n=48) received different dosages of HAM8101 or placebo (n = 8 per group), directly followed by administration of lipopolysaccharide (5 mg/kg). Twenty-four hours later, Evans Blue dye was administered to assess vascular leakage in kidney and liver tissue. Furthermore, mice (n = 24) were administered different dosages of HAM8101 or placebo (n = 6 per group), immediately followed by cecal ligation and puncture (CLP). Eighteen hours later, albumin, vascular endothelial growth factor (VEGF), and angiopoietin-1 were analyzed in the kidney. Finally, effects of single and repeated dose administration of HAM1101, HAM8101 and placebo on survival were assessed in CLP-induced murine sepsis (n = 60, n = 10 per group).

Results: Dosages of 0.1 and 2.5 mg/kg HAM8101 attenuated renal albumin leakage in endotoxemic rats. Dosages of 0.1, 2.0, and 20 mg/kg HAM8101 reduced renal concentrations of albumin and the detrimental protein VEGF in septic mice, whereas concentrations of the protective protein angiopoietin-1 were augmented. Both single and repeated administration of both HAM1101 and HAM8101 resulted in improved survival during murine sepsis.

Conclusions: Pretreatment with the humanized anti-ADM antibody HAM8101 improved vascular barrier function and survival in rodent models of systemic inflammation and sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / antagonists & inhibitors*
  • Adrenomedullin / immunology*
  • Animals
  • Antibodies / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cecum / injuries
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Kidney / drug effects
  • Kidney / metabolism
  • Ligation / adverse effects
  • Male
  • Mice
  • Punctures / adverse effects
  • Rats
  • Rats, Wistar
  • Sepsis / drug therapy*
  • Sepsis / immunology


  • Antibodies
  • Antibodies, Monoclonal, Humanized
  • Adrenomedullin