Table 1.
Most representative preclinical studies addressing trauma, HS and sepsis, respectively.
| Model | Intervention | Outcome | References | |
|---|---|---|---|---|
| Trauma | Mouse TBI | CR2-fH: C3 deposition Inhibition |
Less C3 deposition in brain; decreased microglia activation; less neuronal cell death |
(71) |
| Mouse TBI | C6 antisense oligonucleotide Inhibition of MAC formation Coversin (OMCI) C5 inhibition |
Inhibition of C6: less cerebral MAC (up to 96%); inhibition of C6 synthesis (> 80%) | (72) | |
| Mouse TBI | CD59-2a-CRIg Terminal pathway (MAC) inhibition |
Less axonal damage; enhanced neurological recovery; inhibition of C5: decreased MAC formation; improved neurological outcome |
(73) | |
| Mouse TBI | CR2-CD59: Terminal pathway (MAC) inhibition CR2-Crry: all complement pathways inhibition CR2-fH: alternative complement pathway inhibition |
Significantly improved chronic outcomes | (74) | |
| Sepsis | Baboon septic shock |
RA101295: C5 inhibition | Significantly improved survival; reduced inflammation and coagulopathy; significantly improved organ function |
(75) |
| Mouse meningococcal sepsis |
PMX 205: C5aR antagonist | Protection from invasive meningococcal infection; enhanced mouse survival; ameliorated inflammatory cytokine response |
(76) | |
| Piglets poly-microbial sepsis |
Coversin (OMCI) C5 inhibition And Anti-CD14 |
Combined C5 and CD14 inhibition: significantly improved survival; significantly lower plasma sC5b-9 levels, which correlated with mortality | (77) | |
| Baboon septic shock |
Compstatin: C3 inhibition | Significantly decreased procoagulant response; organ protection by significantly improved vascular barrier function; less leukocyte infiltration and cell death |
(5) | |
| HS | NHP HS |
Comstatin C3 blockade | Protection of organ function; reduced intestinal edema; improved kidney function | (78) |
| Swine trauma with HS | C1 inhibition | less TNF; less complement deposition[C3, C5 and C5b-9 (MAC)] in the small intestine and lungs; improvement of metabolic acidosis; less renal, intestinal, and lung tissue damage | (79) |
HS, hemorrhagic shock; MAC, membrane attack complex; NHP, non-human primate; TBI, traumatic brain injury; TNF, tumor necrosis factor.