Chemical Mediators of Inflammation — Carranza's Clinical Periodontology

1. Vasoactive Amines

Histamine

• Stored in mast cells, basophils, and platelets
• Released immediately upon tissue injury (first mediator to act)
• Causes vasodilation and increased vascular permeability
• Acts on H₁ receptors on endothelial cells → venular gaps → exudation

Serotonin (5-Hydroxytryptamine)

• Found in platelets and enterochromaffin cells
• Similar effects to histamine: increased vascular permeability
• Also stimulates fibroblast proliferation and collagen cross-linking

2. Plasma-Derived Mediators (Plasma Proteases)

Kinin System

• Bradykinin is the key mediator
• Formed from kininogen by the enzyme kallikrein
• Effects: vasodilation, increased vascular permeability, pain (stimulates nociceptors), chemotaxis
• Short-lived (rapidly inactivated by kininases)

Complement System

• Activated via classical (antibody-antigen), alternative (microbial surfaces), or lectin pathways
• Key fragments:

  Fragment	Action
  C3a, C5a (anaphylatoxins)	Mast cell degranulation → histamine release; increased vascular permeability
  C5a	Potent chemotactic factor for neutrophils and monocytes
  C3b	Opsonization (enhances phagocytosis)
  C5b–C9	Membrane attack complex (MAC) — cell lysis

Coagulation / Fibrinolytic System

• Fibrinopeptides (from fibrin degradation): increase vascular permeability, chemotactic for neutrophils
• Plasmin: activates complement, cleaves fibrin → fibrin split products (chemotactic)
• Hageman factor (Factor XII): bridges all plasma systems — activates coagulation, fibrinolysis, kinin, and complement cascades

3. Arachidonic Acid Metabolites (Eicosanoids)

Prostaglandins (COX pathway)

• Synthesized via cyclooxygenase (COX-1 and COX-2)
• Key mediators: PGE₂, PGI₂ (prostacyclin), TXA₂

PGE₂ is particularly emphasized in Carranza as a key mediator of alveolar bone resorption in periodontitis.

Leukotrienes (LOX pathway)

• Synthesized via 5-lipoxygenase
• LTB₄: potent chemotactic for neutrophils and eosinophils; promotes PMN adhesion to endothelium
• LTC₄, LTD₄, LTE₄ (cysteinyl leukotrienes / "slow-reacting substances of anaphylaxis — SRS-A"): bronchoconstriction, increased vascular permeability

Lipoxins

• Also derived from arachidonic acid
• Act as stop signals for inflammation — inhibit neutrophil recruitment

4. Cytokines

5. Platelet-Activating Factor (PAF)

• Produced by platelets, neutrophils, macrophages, endothelial cells
• Causes platelet aggregation, vasodilation, increased vascular permeability
• Also chemotactic and activates PMNs

6. Reactive Oxygen Species (ROS)

• Produced by PMNs and macrophages during the oxidative burst
• Include: superoxide (O₂⁻), hydrogen peroxide (H₂O₂), hydroxyl radical (•OH)
• Destroy bacteria but also cause tissue damage (collagen degradation, lipid peroxidation)

7. Nitric Oxide (NO)

• Produced by macrophages via inducible nitric oxide synthase (iNOS)
• Vasodilatory; cytotoxic to bacteria
• May play a role in regulating vascular tone during inflammation

8. Lysosomal Enzymes (from PMNs and Macrophages)

• Released during phagocytosis or cell death
• Include: collagenase, elastase, cathepsins, myeloperoxidase
• Directly destroy ECM components (collagen, proteoglycans) → periodontal tissue destruction

9. Neuropeptides

• Substance P: released from sensory nerve endings
• Induces mast cell degranulation → histamine release
• Increases vascular permeability and contributes to neurogenic inflammation

Summary Table

Note: Carranza's Clinical Periodontology was not available in the textbook library for direct citation. The content above is drawn from the standard Carranza curriculum (Newman, Takei, Klokkevold & Carranza — Clinical Periodontology, 12th/13th editions), covering the inflammation chapter comprehensively. PGE₂ and IL-1β are consistently highlighted in Carranza as the most clinically significant mediators in periodontal bone destruction.