Table 1.
Pharmacological therapies for sterile inflammation and their associated mechanisms.
| Intervention | Mechanism | Species | Findings | Reference |
|---|---|---|---|---|
| Thrombomodulin | TLR-4/NF-κB/HMGB1 axis (inhibitor) | Mouse | Decreased expression of HMGB-1, downregulated caspase 3 expression and apoptosis, upregulated Bcl-2 (anti-inflammatory) | (168) |
| Dexmedetomidine | TLR-4/NF-κB/HMGB1 axis (inhibitor) | Rats | Decreased expression of cellular NF-κB, TLR-4, serum TNF-α, IL-1β, and myeloperoxidase | (169) |
| rhRelaxin | Apoptotic HMGB1 release (inhibitor) | Mouse | Reduced apoptosis frequency and caspase 3 expression, increased Bcl-xL/Bcl-2 expression, suppressed HMGB1 release | (24) |
| ML355 | MAPK/NF-κB (inhibitor) | Mouse, porcine, non-human primate | Downregulation of proteins involved in MAPK pathway specific to the liver [12-hydroxyeicosatetraenoic acid (12-HETE)] and NF-κB | (170) |
| Dual specificity phosphatase 14 (Dusp14) | TAK1/Jnk1 TAK1/NF-κB (inhibitor) | Mouse | Decreased frequency of necrotic tissue, decreased neutrophil and macrophage infiltration, downregulation of caspase 3, downregulation of proinflammatory cytokines, upregulation of Bcl-2/Bcl-xL | (171) |
| mTOR (knockout model) | mTOR/NF-κB axis (prevents dysregulation) | Mouse | Decreased expression of caspase 3 and frequency of apoptosis, decreased expression of MCP1, TNFα, IL-6 (proinflammatory) cytokines | (172) |
| Omega-3 fatty acids | PI3k/Akt axis (activator) | Rat | Downregulation of NLRP3 and apoptosis, increased expression of glutathione, superoxide dismutase, and catalase (proteins that counteract oxidative stress), decreased expression of malondialdehyde, IL-18 and IL-1β (reflective of inflammation/oxidative stress) | (173) |
| Tanshinone IIa | PI3k/Akt axis (activator) TLR-4/NF-kB/HMGB1 axis (inhibitor) | Rat | Reduced expression of TNFα, IL-4, and HMGB1, lower frequency of cell death, increased expression of IL-10 and TGF-β (anti-inflammatory) | (172) |
| Regulator of G-protein signaling 14 (RGS14) (knockout model) | TAK1/Jnk1/p38 MAPK (inhibitor) | Mouse | Reduced frequency of cell necrosis, apoptosis (caspase 3 cleavage), and infiltrating immune cells, downregulation of Bcl-2 with upregulation of Bad and Bax, downregulation of inflammatory kines MCP1, TNFα, IL-1β | (174) |
| Serelaxin | Notch1 (activator) | Mouse | Reduced expression of MCP1, IL-1β, CXCL10, CXCL2 (inflammatory cytokines), markedly reduced immune cell infiltration, reduced frequency of apoptotic cells | (24) |
| Heme oxygenase 1 (knockout Model) | Heme oxygenase-1/sirtuin1/p53 axis | Mouse, human | Human: decreased caspase 3 cleavage (apoptotic frequency) Mouse: decreased macrophage activation, decreased MCP1, TNFα expression |
(35) |