Inflammation Overview and Key Mediators

Mediators of Inflammation

  • Vasoactive Amines:

    • Histamine:

    • Source: Mast cells, basophils, platelets

    • Action: Vasodilation, increased vascular permeability, endothelial activation

    • Triggers: Allergic reactions via IgE, anaphylatoxins, physical injury, neuropeptides (e.g., substance P)

    • Inhibitors: H1 blockers (cetirizine), H2 blockers (omeprazole)

    • Serotonin:

    • Source: Present in platelets and neuroendocrine cells

    • Action: Primarily a vasoconstrictor, role in inflammation unclear

  • Arachidonic Acid Metabolites:

    • Eicosanoids:

    • Derived from arachidonic acid (AA), produced by phospholipase A2, activated by inflammatory stimuli.

    • Types include Prostaglandins (PG), Leukotrienes (LT), and Thromboxanes (TX).

    • COX-1 and COX-2 proliferation leads to various effects such as vasodilation, pain, and fever.

    • Production Pathways:

    • Cyclooxygenase (COX): Produces prostaglandins and thromboxanes - responsible for vasodilation, inhibition of platelets, and increased vascular permeability.

      • Inhibitors: Aspirin (irreversible), NSAIDs (reversible).

    • Lipoxygenase: Produces leukotrienes, mediates bronchoconstriction and increases vascular permeability.

      • Inhibitors: Specific leukotriene receptor antagonists (e.g., Montelukast) are used to treat bronchoconstriction.

  • Cytokines:

    • TNF-α, IL-1, IL-6: Produced by macrophages, endothelial cells; they promote leukocyte adhesion, migration, and systemic effects like fever and acute phase protein synthesis.
    • Chemokines: Act as chemoattractants, directing leukocyte movement.

Clinical Signs of Inflammation

  • Cardinal Signs:
    • Redness, heat, swelling, pain, loss of function.
  • Systemic Responses:
    • Fever: Pyrogens stimulate IL-1 and TNF release, increasing COX activity and resulting in PGE2 elevation, altering hypothalamic set point.
    • Leukocytosis: Increase in leukocyte count based on type of infection:
    • Viral: Lymphocytes
    • Bacterial: Neutrophils
    • Parasitic: Eosinophils
  • Acute Phase Reactants (APRs):
    • Positive APRs: Elevated during inflammation (e.g., C-reactive protein (CRP), fibrinogen).
    • Negative APRs: Decline during inflammation (e.g., Albumin).

Laboratory Investigations

  • Erythrocyte Sedimentation Rate (ESR): Indicates inflammation; influenced by fibrinogen; elevated in various conditions.
  • CRP: Rapid increase in response to inflammation; useful for assessing bacterial infection specificity.

Complement System

  • Comprised of 20 serum proteins activated in response to infection; can be triggered by classical, lectin, or alternative pathways.
  • Acts in both innate and adaptive immunity to promote inflammation, opsonization, and lysis of pathogens.

Pharmacologic Inhibitors

  • NSAIDs: Provide anti-inflammatory effects by inhibiting COX enzymes, reducing eicosanoid production.
    • Examples include ibuprofen, naproxen, and aspirin.
  • Corticosteroids: Inhibit phospholipase A2, preventing the release of arachidonic acid and subsequent synthesis of inflammatory mediators.

Conclusion and Key Points

  • Inflammation serves a critical protective role but can lead to significant pathology when dysregulated.
  • Understanding mediators, their sources, and physiological effects is essential for diagnosing and managing inflammatory conditions effectively.
  • Monitoring levels of APRs and cytokines can guide clinical decision-making and treatment strategies.