C O N T E N T SSee AlsoDescriptionCytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced de novo in response to an immune stimulus. They generally (although not always) act over short distances and short time spans and at very low concentration. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior (gene expression). Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation, and secretion of effector molecules. Non-nutrient environmental factors affecting cytokine concentrationFrom Kaput and Rodriguez (1)
DiscussionCytokine blocking has had some clinical applications, including the use of Etanercept, a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human p75 TNF-alpha cellular receptor linked to the Fc portion of human immunoglobulin (Ig)G1 for the treament of Alzheimer's dementia. Etanercept specifically binds to TNF-alpha, rendering it biologically ineffective.(2) Remicade (infliximab), also a TNF-alpha agonist, has been shown to have effectiveness in a variety of inflammatory conditions, including rheumatoid arthritis, ulcerative colitis and psoriasis. (3) Cytokine activity decreases over time in stored blood. (4) There is an expanding body of clinical and experimental evidence that cytokines, especially interleukin-1, tumor necrosis factor, interleukin-6, and interleukin-8, are principle mediators of immune responses to erythrocyte incompatibility. Recent studies have further suggested that the monocyte chemotactic and activating factor, monocyte chemoattractant protein-1, and the anti-inflammatory cytokine interleukin-1 receptor antagonist are produced in experimental models of hemolytic transfusion reactions. Differing levels and patterns of expression of these cytokines may be seen in models of intravascular hemolysis due to ABO incompatibility and extravascular hemolysis due to Rh incompatibility, which correlate with the recognized clinical differences between these two types of reactions. (5)
LinksReferences1. Kaput J. An introduction and overview of nutritional genomics: Application to type 2 diabetes and international nutrigenomics. In: From Kaput J and Rodriguex R. Nutritional Genomics. 2006 Wiley 2. Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed. 2006;8(2). 3. Penn H. Biologic therapies in autoimmune diseases. Clin Med. 2006 Jan-Feb;6(1):105-8. 4. Mynster T, Dybkjoer E, Kronborg G, Nielsen HJ. Immunomodulating effect of blood transfusion: is storage time important? ox Sang. 1998;74(3):176-81. 5. Davenport R. Cytokines and erythrocyte incompatibility.Curr Opin Hematol. 1994 Nov;1(6):452-6. |