Acute Phase Inflammatory Proteins - Acute Phase Reactants

Acute Phase Inflammatory Proteins - Acute Phase Reactants

 

Plasma proteins termed acute phase inflammatory  proteins or reactants are involved in the innate system’s response to inflammation, tissue injury or malignancy.  During the inflammatory process, the plasma concentration of these acute phase proteins increases or decreases by at least 50%.

Alpha-1-acid glycoprotein

  • Produced by hepatocytes into the blood in response to physical trauma, infection, wounding
  • Regulated – by proinflammatory cytokines that include interleukin 1 (IL-1), interleukin 6 (IL-6), chemokines (IL-8) and glucocorticoids
  • Stimulates immunomodulatory activity that may reduce collateral damage caused by inflammation

Cytokines

  • Cytokines are integrally involved in inflammatory reactions
  • Interleukins are cytokines that act as mediators between leukocytes.  There are 18 identified interleukins with varying effects

 

Human Plasma Acute Phase Proteins
Positive Acute Phase Proteins

Complement system

C3, C4, C9, Factor B, C1 inhibitor, C4b-BP, Mannose-BP

Coagulation system

Fibrinogen, Plasminogen, Urokinase, Protein S, Vitronectin, PAI-1

Antiproteases

Alpha 1-Protease inhibitor, alpha-1-antichymotrypsin, Pancreatic secretory trypsin inhibitor, Inter-alpha-trypsin inhibitor

Binding Proteins

Ceruloplasmin, Haptoglobin, Hemopexin, LPS-BP

Proteins involved in inflammatory response

Secreted phospholipase A2, IL-IRA, GM-CSF

Others

Serum amyloid A, C-reactive protein, ACP, Fibronectin, Ferritin, Angiotensinogen

Negative Acute Phase Proteins

Albumin, Transferrin, alpha 2-HS-Glycoprotein, alpha-fetoprotein, Thyroxine-BP, IGF-1,Factor XII
(Used with permission from Ceciliani, 2007, 91)

Tumor necrosis factor (TNF-α, cachectin)

  • Produced by mononuclear phagocytes
  • In vitro activities attributed to TNF-α  
    • Activation of T-cells 
    • Pyrogenicity and endotoxemia
    • Mitogenic effects on fibroblasts 
    • Resorption of bone and cartilage
    • Activation of neutrophil function 
    • Decreased activity of several enzymes involved in lipid metabolism
    • Decreased synthesis of hepatic protein
    • Cachexia
    • Induction of
      • Interleukin-6 (IL-6), Interleukin-1 (IL-1) and Interleukin-2 (IL-2) receptors
      • Granulocyte monocyte-colony stimulating factor (GM-CSF)
      • C-myc and c-fos genes
      • Epidermal growth factor (EGF)

Cytokines

  • Interleukin-6
    • A glycoprotein produced by activated T-cells
    • Involved in B-cell differentiation into plasma cells
      • Usually not detected in normal serum, plasma, cerebral spinal fluid (CSF) or joint fluid
    • Elevated levels occur in
      • Inflammatory processes
        • Infections (endotoxemia)
        • Collagen vascular diseases
      • Alcoholic cirrhosis
      • Chronic renal failure
      • Central nervous system inflammation (increased CSF levels)
        • Bacterial meningitis
        • Central nervous system (CNS) involvement in systemic lupus erythematosus
      • Rheumatoid arthritis (increased synovial fluid levels)
  • Interleukin-2
    • A glycoprotein produced by activated T-cells
    • Also known as:
      • T-cell growth factor
      • Thymocyte simulation factor (TSF)
      • Thymocyte mitogenesis factor (TMF)
      • T-cell replacing factor (TRF)
      • Killer-helper factor (KHF)
    • Most notable immunologic function is the activation, proliferation and promotion of:
      • T-cells
      • B-cells
      • Natural killer cells (NK cells)
    • Decreased IL-2 production associated with:
      • Systemic lupus erythematosus (SLE)
      • Hodgkin lymphoma
      • Lepromatous leprosy
      • AIDS
      • Common variable hypogammaglobulinemia
      • Chronic mucocutaneous candidiasis 

Interleukin-1-beta

  • Produced by activated macrophages
  • Mediates a wide variety of biological actions
    • Stimulates expression of IL-2 receptors
    • Stimulates production and secretion of IL-2
  • In synergy with tumor necrosis factor alpha, elevated interleukin-1-beta is seen in:
    • Septic shock
    • Cerebrospinal fluid
      • Meningitis
      • Multiple sclerosis

Interleukin-8

  • Produced by activated macrophages
  • Pro-inflammatory cytokine and chemoattractant for neutrophils
  • Elevated levels observed in many inflammatory processes, including infections and connective tissue diseases

See Also