Wound Care: Mediators of Wound Healing

Colony-Stimulating Factors

• Macrophage Colony-Stimulating Factor (M-CSF)
  • Stimulates Hematopoietic Stem Cell Differentiation into Macrophages
• Granulocyte Colony-Stimulating Factor (G-CSF)
  • Stimulates Hematopoietic Stem Cell Differentiation into Granulocytes (Neutrophils, Eosinophils and Basophils)
• Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
  • Stimulates Hematopoietic Stem Cell Differentiation into Granulocytes (Neutrophils, Eosinophils and Basophils) & Monocytes/Macrophages

Transforming Growth Factors

• Transforming Growth Factor Alpha (TGF-α)
  • Produced by Macrophages, Brain Cells & Keratinocytes
  • Induces Epithelial Development – Similar to EGF
• Transforming Growth Factor Beta (TGF-β)
  • Produced by Macrophages and All Leukocytes
  • Anti-Inflammatory Effects:
    • Regulates Lymphocyte Proliferation, Differentiation & Survival
    • Inhibits Synthesis of Proinflammatory Cytokines
    • Inhibits Function of Natural Killer Cells, Dendritic Cells & Macrophages

Other Growth Factors

• Fibroblastic Growth Factor (FGF)
  • Produced by Macrophages
  • Numerous Functions in Regulating Cell Proliferation, Migration & Differentiation
• Epidermal Growth Factor (EGF)
  • Secreted by Salivary Glands
  • Stimulates Growth of Epidermal & Epithelial Cells
• Vascular Endothelial Growth Factor (VEGF)
  • Promotes Angiogenesis
• Platelet Derived Growth Factor (PDGF)
  • Secreted by Platelets
  • Attracts & Activates Inflammatory Cells & Fibroblasts
  • Promotes Wound Healing

Cytokines

• Tumor Necrosis Factor Alpha (TNF-α)
  • Produced by Macrophages
  • Increases Adhesion & Coagulation
  • Activates Neutrophils & Macrophages
  • Causes Cachexia in Cancer Patients
• Erythropoietin (EPO)
  • Secreted in the Kidney Due to Cellular Hypoxia
    • Fetal Production Primarily in the Liver
  • Stimulates Erythropoiesis (RBC Development)

Interleukins

• IL-1
  • Strong Proinflammatory Effects
  • Causes Fever
    • Increased Prostaglandin E2 in Hypothalamus Raises Thermal Set-Point
    • NSAIDs Decrease Fever by Lowering PGE2 Levels
  • Activates Helper T Cells
• IL-2
  • Released by Helper T Cells
  • Stimulates Differentiation/Maturation of Cytotoxic T Cells
• IL-3
  • Stimulates Hematopoietic Stem Cell Differentiation & Proliferation
  • Causes Mast Cell Growth & Histamine Release
• IL-4
  • Released by Helper T Cells
  • Stimulates Differentiation/Maturation of B Cells into Plasma Cells
• IL-5
  • Overproduction Activates Eosinophils (Induces Allergies and Asthma)
• IL-6
  • Stimulates Hepatic Acute Phase Response (Increased CRP & Amyloid A)
  • Stimulates Hematopoietic Stem Cell Differentiation
  • Stimulates Differentiation of B Cells into Plasma Cells & Plasma Cell Antibody Secretion
• IL-7
  • Induces Differentiation & Proliferation of Lymphoid Progenitor Cells
  • Increases Proinflammatory Cytokines
• IL-8
  • PMN Chemotaxis & Angiogenesis
• IL-9
  • Released by Helper T Cells
  • Potentiates Select Ig Cells
• IL-10
  • Inhibits Inflammatory Response