Table 2.
Soluble mediators and their role in adhesion formation.
| Signaling Molecule | Brief Role in Adhesions |
|---|---|
| Fibrin | Disruption of fibrin production and fibrinolysis homeostasis Formation of polymeric matrix for cellular adhesion and ECM production Scaffold for fibroblasts and capillary formation ↑ plasminogen activation |
| Tissue plasminogen activator (tPA) | Regulation of fibrinolytic system ↓ plasma levels in rat peritoneal adhesion model |
| Plasminogen activator inhibitor (PAI) | Inhibit tissue plasminogen activator, ↓ fibrinolysis ↑ plasma levels in rat peritoneal adhesion model |
| Reactive Oxygen Species (ROS) | Enhanced in peritoneal adhesion Direct cytotoxic effect on mesothelial cells Inhibit fibrinolysis through PAI-1 release in mesothelial cells Treatment by ROS scavengers reduces adhesion formation |
| Chymase | Activates profibrotic TGF-β |
| IL-6 | Marker for early tissue damage Promotes fibrosis via MMP and TIMP expression ↑ in intra-abdominal adhesion models ↑ in human adhesions 12 h associated with reformation ↑ directly correlated with extent of adhesion formation Inhibition in mouse model ↓ adhesion formation Stimulate mesothelial and inflammatory cells to ↑ PAI-1/2 |
| IL-8 | Neutrophil chemo-attractant |
| IL-10 | Modulates macrophage and lymphocyte responses Inhibit secretion of pro-inflammatory mediators ↑ in adhesion fibroblasts |
| IL-1 | Early elevations are biological marker ↑ IL-1 in human adhesions at 48 h ↓ local fibrinolytic capacity IL-1β increases release of PAI-1 ↓ fibrinolysis |
| IL-17 | Peak levels 6–12 h after surgery ↑ IL-17 ↑ PAI-1 and ↓ tPA |
| IFN-γ | Necessary for adhesion development ↑ PAI-1 and ↓ tPA |
| TNF-α | ↑ directly correlated with extent of adhesion formation ↑ IL production |
| TGF-β | Principal fibrotic mediator ↑ in adhesion tissue, peritoneal fluid, and animal models ↓ reduces incidence, quality, and tenacity of adhesions |
| VEGF | Increases vascular permeability Promotes deposition of fibrin matrix ↑ in endothelial cells in pelvic adhesions ↓ reduces adhesions |
| MMP and TIMP | MMP-2/9 proposed as biomarkers MMP/TIMP ratio alterations decrease enzymatic activity Inactivating MMP results in reduction of severity Blocking TIMP-1 prevents primary adhesion formation |
| Substance P | ↓ fibrinolytic activity |
| Serotonin | ↑ inflammation, oxidative stress, angiopoiesis ↑ TGF-β expression Regulation of fibrinolytic system |
ECM = extracellular matrix, IFN-γ = interferon-gamma, IL = interleukin, PAI = plasminogen activator inhibitors, tPA = tissue plasminogen activator, ROS = reactive oxygen species, TGF-β = transforming growth factor-beta, TNFα = tumor necrosis factor-alpha, VEGF = vascular endothelial growth factor, ↑ = increases, ↓ = decreases.