Interleukins biological activity

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. 

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. 

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. 

Anakinra blocks the biologic activity of IL-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. 

The biological activities of several other interleukins also render them likely candidates for therapeutic application. IL-5 represents one such candidate. IL-5 is a 115 amino acid glycoprotein produced mainly by activated T lymphocytes and also by mast cells. It functions as a homodimer, exhibiting a molecular mass of 45 kDa. The individual polypeptide chains interact non-covalently and the overall dimeric structure is stabilized by two interchain disulphide linkages between cysteines 42 and 84 of each chain. Removal or alterations of the cytokine s carbohydrate side-chain does not appear to affect its biological activity. 

Magnuson, N.S., Linzmaier, P.M., Reeves, R., An, G., HayGlass, K., and Lee, J.M. (1998). Secretion of biologically active human interleukin-2 and inter-leukin-4 from genetically modified tobacco cells in suspension culture. Protein Exp. Purif. 13(1) 45-52. 

The interactions between immune and inflammatory cells are mediated in large part by certain proteins, called lym-phokines, or interleukins (IL), that are able to promote cell growth, differentiation, and functional activation. Interleukins resemble hormones, which also function as intercellular messengers. In contrast to hormones, however, they are secreted by isolated cells rather than discrete glands. Several interleukins have been described each has unique biological activities as well as some that overlap with the oth-... 

Cranath, W.O. Jr, Connors, V.A. and Tarleton, R.F. (1 994) Interleukin 1 activity in haemolymph from strains of the snail Biomphalaria glabrata varying in susceptibility to the human blood fluke, Schistosoma mansoni presence, differential expression, and biological function. Cytokine 6, 21-2 7. 

Zitvogel, L., Tahara, H., Cai, Q., Storkus, W.J., Muller, G., Wolf, S.F. etal. (1994) Construction and characterization of retroviral vectors expressing biologically active human interleukin-12. Hum. Gene Then, 5, 1493-1506. 

Hofer et al. [74-76] designed and characterized transfersomes with immunomodulators interleukin-2 (IL-2) and INF-a and reported that both molecules retained their biological activity and could be efficiently encapsulated in these vesicles. 

Oshima, Y., and Puri, R. K., Characterization of a powerful high affinity antagonist that inhibits biological activities of human interleukin-13. J. Biol. Chem 276,15185-15191 (2001). 

Another cytokine class used as a biopharmaceutical is interleukin (IL), which consists of at least 25 different subtypes (IL-1 to IL-25). Except for IL-1, most interleukins are glycosylated and have a molar mass in the range of 15-30 kDa. IL-2 is the most well studied interleukin, and its recombinant form is approved for the treatment of renal cell carcinoma. Since the absence of glycosylation does not affect its biological activity, rIL-2 is produced in genetically engineered E. coli. 

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