Acute Phase Proteins - Acute Phase Reactants

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Inflammation or infection not explained by other etiology

Laboratory Testing

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

Classification

Pathophysiology

  • Most acute phase reactants are synthesized in the hepatocytes
    • Not elevated in functional disturbances
    • Usually not elevated in stable chronic diseases
    • Strongly elevated in bacterial infections, juvenile arthritis, tumors, Crohn disease, surgery, polymyalgia rheumatica, systemic vasculitis, burns, fractures
    • Negligible elevation in arthralgia, myalgia, back pain

Selected Acute Phase Proteins

  • Alpha-1 acid glycoprotein
    • Function – immunomodulatory activity that may reduce collateral damage caused by inflammation
    • Regulation – proinflammatory cytokines, (eg, interleukin 1 (IL-1), interleukin 6 (IL-6), chemokines (IL-8), glucocorticoids)
  • Pentraxins
    • C-reactive protein (CRP)
      • Functions
        • May increase a thousand fold in response to inflammation and infection
        • Acts as an opsonin for bacteria, parasites, immune complexes
          • Can act as an activator of classic complement pathway
        • Elevated in many disease states (eg, coronary artery disease, infections, vasculitis, acute phase of connective tissue diseases, malignancy)
    • Amyloid
      • Functions
        • Apolipoproteins that associate with HDL3
        • Enhances binding capacity of HDL3 to hepatocytes
        • Elevated in malignancy
    • Haptoglobin
      • Functions
        • Binds free hemoglobin released from erythrocytes
        • Involved in inflammation, infections, malignancy
    • Ceruloplasmin
      • Functions
        • Globulin involved in release of iron into plasma cells
        • Serum antioxidant
        • Modulates inflammatory response
        • Elevated in pregnancy, high estrogen conditions, infections, cirrhosis, malignancy, hyperthyroidism, rheumatoid arthritis (RA)
  • Cytokines
    • Functions
      • Major activators of acute phase proteins are IL-1 and IL-6
      • Mediators between leukocytes – 18 identified interleukins with varying effects
    • Interleukin-1-beta
      • Production – activated macrophages
      • Functions – 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 the following
    • Interleukin-6
      • Function – 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 the following
        • Inflammatory processes
          • Infections – endotoxemia
          • Connective tissue disease
        • Alcoholic cirrhosis
        • Chronic renal failure
        • Central nervous system inflammation – increased CSF levels
        • RA – increased synovial fluid levels
    • Interleukin-2
      • Production – activated T cells
      • Also known as
        • T-cell growth factor
        • Thymocyte simulation factor
        • Thymocyte mitogenesis factor
        • T-cell replacing factor
        • Killer-helper factor
      • Function – most notable immunologic function is the activation, proliferation, and promotion of T cells, B cells, NK cells
      • Decreased IL-2 production associated with
    • Interleukin-8
      • Production – activated macrophages
      • Function – proinflammatory cytokine, chemoattractant for neutrophils
      • Elevated in many inflammatory processes – infections, connective tissue diseases
  • Tumor necrosis factor (TNF-α, cachectin)
    • Production – mononuclear phagocytes
    • Functions
      • 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
    • Regulation
      • IL6R, IL1R, and IL2RA interleukin receptors
      • Granulocyte monocyte-colony stimulating factor
      • MYC and FOS genes
      • Epidermal growth factor

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Additional Tests Available

Alpha-1-Acid Glycoprotein 0050002
Method: Quantitative Nephelometry

Comments

Limited clinical use

Haptoglobin 0050280
Method: Quantitative Immunoturbidimetry

Comments

Limited clinical use

Tumor Necrosis Factor - alpha 0051539
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Panel 12 0051394
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Panel, Monokines 0051524
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Interleukin 1 beta 0051536
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Interleukin 2 Receptor (CD25), Soluble 0051529
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Interleukin 2 0051588
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Interleukin 6 0051537
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Interleukin 8 0051538
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Alpha-1-Antitrypsin 0050001
Method: Quantitative Immunoturbidimetry

Comments

Limited clinical use

Cytokine Panel, TH1 0051408
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Panel, TH2 0051518
Method: Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, 12 Cytokines (INACTIVE as of 04/04/16: Refer to February 2016 Hot Line for Replacement Test: 2013109, ACTIVE 04/04/16) 0051540
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interferon gamma (INACTIVE as of 04/04/16) 0051574
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 1 beta (INACTIVE as of 04/04/16) 0051580
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 2 (INACTIVE as of 04/04/16) 0051571
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 2 Receptor (CD25), Soluble (INACTIVE as of 04/04/16) 0051572
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 4 (INACTIVE as of 04/04/16) 0051576
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 5 (INACTIVE as of 04/04/16) 0051577
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 6 (INACTIVE as of 04/04/16) 0051581
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response to Mitogens, Monokines (INACTIVE as of 04/04/16) 0051587
Method: Cell Culture/Multiplex Bead Assay

Comments

Limited clinical use

Toll-Like Receptor Function 0051589
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Assist in diagnosis of innate immunodeficiencies when genetic defects of the innate immune system are suspected in individuals negative for other immunodeficiencies (eg, no detectable abnormality of antibody function, complement activity, neutrophil function, or cell mediated immunity)

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 8 (INACTIVE as of 04/04/16) 0051582
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Tumor Necrosis Factor alpha (INACTIVE as of 04/04/16) 0051583
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 10 (INACTIVE as of 04/04/16) 0051578
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Cytokine Production by Mononuclear Cells in Response to Mitogen Stimulation, Interleukin 13 (INACTIVE as of 04/04/16) 0051579
Method: Cell Culture/Quantitative Multiplex Bead Assay

Comments

Limited clinical use

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

General References

Ceciliani F, Pocacqua V. The acute phase protein alpha1-acid glycoprotein: a model for altered glycosylation during diseases. Curr Protein Pept Sci. 2007; 8(1): 91-108. PubMed

Correale M, Brunetti N, De Gennaro L, Di Biase M. Acute phase proteins in atherosclerosis (acute coronary syndrome). Cardiovasc Hematol Agents Med Chem. 2008; 6(4): 272-7. PubMed

Filip Z, Jan K, Vendula S, Jana K, Kamil M, Kamil K. Albumin and α1-acid glycoprotein: old acquaintances. Expert Opin Drug Metab Toxicol. 2013; 9(8): 943-54. PubMed

Malle E, Sodin-Semrl S, Kovacevic A. Serum amyloid A: an acute-phase protein involved in tumour pathogenesis. Cell Mol Life Sci. 2009; 66(1): 9-26. PubMed

Rehman A, Ahsan H, Khan F. α-2-Macroglobulin: a physiological guardian. J Cell Physiol. 2013; 228(8): 1665-75. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

La Pine T, Joyner J, Augustine N, Kwak S, Hill H. Defective production of IL-18 and IL-12 by cord blood mononuclear cells influences the T helper-1 interferon gamma response to group B Streptococci. Pediatr Res. 2003; 54(2): 276-81. PubMed

Martins T, Pasi B, Litwin C, Hill H. Heterophile antibody interference in a multiplexed fluorescent microsphere immunoassay for quantitation of cytokines in human serum. Clin Diagn Lab Immunol. 2004; 11(2): 325-9. PubMed

Martins T, Pasi B, Pickering J, Jaskowski T, Litwin C, Hill H. Determination of cytokine responses using a multiplexed fluorescent microsphere immunoassay. Am J Clin Pathol. 2002; 118(3): 346-53. PubMed

Medical Reviewers

Last Update: February 2016