Biologies interleukin

The discovery of novel chemokines essentially occurred in three waves. First of all, many chemokines were purified from cell culture media, or leukocyte exudates. These were the first chemokines to be identified, and include the two mainstays of chemokine biology, Interleukin-8 (IL-8) and Monocyte Chemoattractant Protein-1 (MCP-1). It is interesting that chemokines could indeed be purified in this way, compared with other cytokines, which have tended to be identified initially as cDNAs. One of the reasons that chemokines... 

Boch, J. A., Wara-Aswapati, N., and Auron, P. E. 2001. Concise review biological Interleukin 1 signal transduction—Current concepts and relevance to periodontitis. Journal of Dental Research, 80,400. 

This drug also is reported to activate macrophages, to iaduce polyclonal B-ceU activation as well as enhance specific antibody production m vivo, and to iaduce the synthesis of iaterferon and interleukin 1 (52). The iaduction of these important cytokiaes (and others) largely accounts for the profile of biological activity displayed by the pyrimidinones. Bropirimine is currentiy ia clinical evaluation for cancer, arthritis, and immunorestoration ia AIDS patients. 

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Recombinant human DL-1 receptor antagonist (Anakinra, Kineret ) blocks the biological activity of interleukin-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. Thereby it reduces the pro-inflammatory activities of IL-1 including cartilage destiuction and bone resorption. Side effects include an increased risk of infections and neutropenia. 

The interleukin-1 (EL-1) family of proteins currently comprises IL-1 a, IL-1 (3, and the IL-1 receptor antagonist (IL-1RA). The biological activities of EL-1 are shared by IL-1 a and IL-1 (3, whereas IL-1RA is a true receptor antagonist. IL-1 is a key player in acute and chronic inflammatory diseases. Whether IL-1 has a role in normal physiology is still unresolved. IL-1 can... 

Kelly, ME, Clay, MA, Mistry, MJ, Hsieh-Li, HM, and Harmony, JA, 1994. Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes Production of interleukin 2 with reduced biological activity. Cell Immunol 159, 124—139. 

McKenzie, G.J., Bancroft, A.J., Grencis, R.K. and McKenzie, A.N.J. (1998b) A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Current Biology 8, 339-342. 

Bennett, B.L., Cruz, R., Lacson, R.G. and Manning, A.M. (1997) Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E-selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB. Journal of Biological Chemistry 272, 10212-10219. 

Lugli, S.M., Feng, N., Heim, M.H., Adam, M., Schnyder, B., Etter, H., Yamage, M., Eugster, H.P., Lutz, R.A., Zurawski, G. and Moser, R. (1997) Tumor necrosis factor alpha enhances the expression of the interleukin (IL)M receptor alpha-chain on endothelial cells increasing IL-4 or IL-13-induced Stat6 activation. Journal of Biological Chemistry 272, 5487-5494. 

Bogdan, C., Paik, J., Vodovotz, Y. and Nathan, C. (1992) Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. Journal of Biological Chemistry 267, 23301-23308. 

Nearly all of the interleukins are soluble molecules (one form of IL-1 is cell associated). They promote their biological response by binding to specific receptors on the surface of target cells. Most interleukins exhibit paracrine activity (i.e. the target cells are in the immediate vicinity of the producer cells), although some display autocrine activity (e.g. IL-2 can stimulate the growth and differentiation of the cells that produce it). Other interleukins display more systematic endocrine effects (e.g. some activities of IL-1). 

The signal transduction mechanisms by which most interleukins prompt their biological response are understood, in outline at least. In many cases, interleukin cell surface receptor binding is associated with intracellular tyrosine phosphorylation events. In other cases, serine and threonine residues of specific intracellular substrates are also phosphorylated. For some interleukins,... 

The sum total of biological responses induced by the interleukins is large, varied and exceedingly complex. These cytokines regulate a variety of physiological and pathological conditions, including ... 

Devos, R., Plaetinck, G., Cornelis, S., Guisez, Y., Van der Heyden, J., and Tavernier, J. 1995. Interleukin-5 and its receptor a drug target for eosinophilia associated with chronic allergic disease. Journal of Leukocyte Biology 57, 813-818. 

Komschlies, K.L., Grzegorzewski, K.J., and Wiltrout, R.H. 1995. Diverse immunological and haematological effects of interleukin-7 implications for clinical application. Journal of Leukocyte Biology 58, 623-631. 

Krawczenko, A., Kieda, C., and Dus, D. 2005. The biological role and potential therapeutic applications of interleukin 7. Archivum Immunologiae et Therapiae Experimentalis 53(6), 518-525. 

Renauld, J.C., Kermouni, A., Vink, A., Louahed, J., and Van Snick, J. 1995. Interleukin-9 and its receptor involvement in mast cell differentiation and T-cell oncogenesis. Journal of Leukocyte Biology 57, 353-359. 

Sarmiento, U.M. et al., Biologic effects of recombinant human interleukin-12 in squirrel monkeys (Sciureau saimiri), Lab. Invest., 71, 862, 1994. 

Interleukin-1 (IL-1) produced by monocytes and several other cell types [70, 146] has a wide array of biological properties, including T cell activation and inflammatory interactions with muscle, liver, fibroblasts, brain and bone [70, 146], IL-1, both natural and recombinant, has been shown to release histamine from human basophils and from human adenoidal mast cells [70,146,151] and this release was abolished by an IL-1 antibody. However, the average release produced by 10 units of IL-1 was less than 20% and there was considerable variability between populations of basophils in the extent of histamine release. Moreover, the secretory response elicited was quite slow (within 15 min) compared with that of other peptides [151]. Desensitization of the basophils by anti-IgE serum had no effect on the subsequent IL-1 response, suggesting different mechanisms of action [ 151], as has been the case with other peptides. Interestingly, the portion of the IL-1 molecule that is responsible for its immu-nostimulatory activity appears to be separate from that portion responsible for its proinflammatory effects [152]. However, that portion of the molecule responsible for eliciting basophil and mast-cell histamine release has not as yet been defined. 

Brennan, F. M., Zachariae, C. O. C., Chantry, D., Larsen, C. G., Turner, M., Maini, R. N., Matsushima, K., Feldmann, M. (1990). Detection of Interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of Interleukin 8 mRNA by isolated synovial cells. Eur. J. Immunol. 20,2141-4. 

Page, C., P. Dawson, D. Woollacott, R. Thorpe, and A. Mire-Sluis (2000). Development of a lyophilization formulation that preserves the biological activity of the platelet-inducing cytokine interleukin-11 at low concentrations. J Pharm Pharmacol 52(1) 19-26. 

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