The COVID-19 pandemic is still in progress, and a significant number of patients have presented with severe illness. Recently introduced vaccines, antiviral medicines, and antibody formulations can suppress COVID-19 symptoms and decrease the number of patients exhibiting severe disease. However, complete avoidance of severe COVID-19 has not been achieved and there are insufficient methods to treat it. Adrenomedullin (AM) is an endogenous peptide that maintains vascular tone and endothelial barrier function. The AM plasma level is markedly increased during severe inflammatory disorders, such as sepsis, pneumonia, and COVID-19, and associated with its prognosis. Exogenous AM administration reduced inflammation and related organ damage in rodent models. The results strongly suggest that AM could be an alternative therapy for COVID-19. We are currently conducting an investigator-initiated phase 2a trial for moderate to severe COVID-19 using AM.
Genetic Intervention | |||
Animal | Procedure | Results | Reference |
Mouse | AM-deficient (+/−) + LPS-endotoxemia |
compared to WT mice · ↑ mortality · ↑ liver dysfunction |
[58] |
Mouse | AM-deficient (+/−) + LPS-endotoxemia |
compared to WT mice · ↑ TNF-α, IL-1β · ↑ liver dysfunction |
[59] |
Mouse | AM transgenic + LPS-endotoxemia |
compared to WT mice · ↓ BP decline · ↓ organ damage · ↑ survival rate |
[60] |
Exogenous Adrenomedullin Administration | |||
Animal | Procedure | Effects | Reference |
Mouse | Pneumococcal pneumonia + Mechanical ventilation |
· ↓ VILI (pulmonary permeability↓) · ↓ liver and gut injury |
[25] |
Rat | BDL + CLP (obstructive jaundice + polymicrobial sepsis) |
· ↓ tissue injury and inflammatory responses · ↑ survival rate |
[61] |
Rat | Staphylococcus aureus α-toxin induced septic shock | · ↓ translocation of dextran from the gut into the systemic circulation | [62] |
Rat | Cecal ligation and puncture (CLP) | · ↓ tissue injury · ↓ proinflammatory cytokine levels · ↓ intestinal-barrier dysfunction · ↑ survival rate |
[63] |
Sheep | Endotoxin (LPS) infusion | · ↑ cardiac index · ↓ mean pulmonary artery pressure |
[64] |
Rat | Endotoxin (LPS) injection | · ↑ PPER-γ level · ↓ TNF-α |
[65] |
Rat | Intestinal ischemia/reperfusion | · ↓ lung injury · ↓ proinflammatory cytokines |
[66] |
Rat | Staphylococcus aureus α-toxin induced septic shock | · ↓ vascular hyperpermeability · ↑ survival rate |
[67] |
Rat | Intestinal ischemia/reperfusion | · ↓ inflammatory cytokines · ↓ tissue injury · ↑ survival rate |
[68] |
AM: adrenomedullin, LPS: lipopolysaccharide, WT: wild type. TNF: tumor necrosis factor, IF: interferon, BP: blood pressure. VILI: ventilator induced lung injury, BDL: common bile duct ligation. PPER: peroxisome proliferator-activated receptor.
This entry is adapted from the peer-reviewed paper 10.3390/biomedicines10030533