Interleukin sources

Interleukin (from human source). Purified using lyophilisation and desalting on a Bio-Rad P-6DC desalting gel, then two steps of HPLC, first with hydroxylapatite, followed by a TSK-125 size exclusion column. [Kock and Luger J Chromatogr 296 293 7984 ]... 

Buttner C, Skupin A, Reimann T, et al. Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats macrophages as a prominent source of interleukin-4. Am J Respir Cell Mol Biol 1997 17(3) 315-325. 

Scheuerermaly, C.C., Eckmann, L., Kagnoff, M.F., Falco, M.T. and Maly, F.E. (1994) Colonic epithelial cell lines as a source of interleukin-8 stimulation by inflammatory cytokines and bacterial lipopolysaccharide. Immunology 81, 85-91. 

It overcomes the problem of source availability. Many proteins of therapeutic potential are produced naturally in the body in minute quantities. Examples include interferons (Chapter 8), interleukins (Chapter 9) and colony-stimulating factors (CSFs Chapter 10). This rendered impractical their direct extraction from native source material in quantities sufficient to meet likely clinical demand. Recombinant production (Chapters 3 and 5) allows the manufacture of any protein in whatever quantity it is required. 

Source Data from Remmele, R.L., Jr., N.S. Nightlinger, S. Srinivasan, and W.R. Gombotz. 1998. Interleukin-1 receptor (IL-1R) liquid formulation development using differential scanning calorimetry. Pharm Res 15 200-208. 

Figure 4.7 Interleukin 2 (IL-2) molecule. (Source Protein Date Bank, PDB ID 1M47. http //www.rcsb.org/pdb/cgi/explore.cgi job=summary pdbId=lM47 page=. Arkin MM, Randal M, Delano WL, et al. Binding of small molecules to an adaptive protein-protein interface, Proceedings of the National Academy of Sciences USA 100 1603 (2003). Used with permission.)...

Figure 3 Cytokine secretion in immunopotentiating reconstituted influenza viro-somes (IRIV)-stimulated peripheral blood mononuclear cells (PBMC). PBMC from a healthy donor were cultured in the absence of stimuli (Neg) or in the presence of IRIV (V, 1 50 diluted) or control liposomes (L, 1 50 diluted). On days 1, 2, and 4 supernatants were harvested and the concentrations of interferon-y (A), GM-CSF (B), TNF-a (C), and interleukin-4 (D) were determined by ELISA. Abbreviations GM-CSF, granulocyte monocyte colony stimulating factor TNF-a, tumor necrosis factor-a. Source From Ref. 6.

Figure 7 Immunopotentiating reconstituted influenza virosomes (IRIV) mediated adjuvance in cytotoxic T-cell induction requires CD4+ T cells. CD8+ and CD14+ cells were cultured in the presence of autologous intact or irradiated CD4+ cells. These cultures were stimulated with influenza matrix (IM)58 66 (1 Pg/mL) alone (A) or supplemented with IRIV (1 50) (B). After seven days of incubation both cocultures were restimulated with irradiated IMss-ee pulsed CD14+ cells and cultured for six further days in the presence of interleukin-2 [see Materials and Methods ]. Six days after restimulation, cultures were stained with HLA-A0201 /IM58-66 PE-specilic tetramers and anti-CD8 fluorescein isothiocyanate monoclonal antibodies. Source. From Ref 6.

V. CELLULAR SOURCE OF INTERLEUKIN 1-INDUCED NITRIC OXIDE FORMATION BY ISLETS OF LANGERHANS... 

Bradding P, Roberts JA, Britten KM, Montefort S, et al. 1994. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways Evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 10 471—480. 

This technique is performed in tissue culture and works well when only small quantities of antigen (1-2 pg) are available. It also allows the production of antibodies to substances that are toxic in whole animals. There is no immunological processing of antigens so only soluble, simple antigens such as peptides can be used for this approach. A source of interleukins-4 and -5 is required for the method to work and the easiest way of obtaining them is from thymocyte-conditioned medium. 

In an IPCR application developed by Furuya et al. [27], interleukin 18 (IL-18) was studied as an important protein in a number of immunological derangements. An indirect sandwich IPCR (Fig. 3D) was used for the detection of IL-18 in cell culture supernatants and serum samples. A quantitative study of low-level IL-18 was carried out beneath a serum concentration of typically 96 135 ng/L. In a systematic variation of assay conditions, the amount of biotinylated 227-bp DNA marker used in the Universal-IPCR protocol was identified as a source for nonspecific amplification. Following an optimization of DNA concentration and PCR cycle number, 2.5 pg/L IL-18 was detected. 

Glial cells are a source of multiple cytokines, including interleukin-1 /3 (IL-1 /3), IL-6, and tumor necrosis factor-a (Hanisch, 2002). These cytokines can contribute to different features of pathological pain, although their role within the spinal cord has not been completely understood (DeLeo and Yezierski, 2001 Watkins... 

Cytokines and interleukins are proteins produced by a variety of immune and non-immune cells that bind receptors on their target cells and elicit a variety of responses. As of 2008,35 interleukins have been described [23], The principle source of interleukins are immune cells (macrophages and lymphocytes), but they are also produced by a number of immune cells, e.g., Interleukin-6 (IL-6) in a variety of cell types [24], and they are sometimes referred to by the more general term cytokines. Cytokines, because of their ability to affect the activity of a large number of cells and cell types, can amplify an... 

Other components of the innate response include natural killer (NK) cells and a number of cytokines. NK cells lyse certain types of tumor cells and virally infected cells and are a rich source of immune interferon (interferon-y), which stimulates macrophages and T cells hence they are thought to play an important role in host resistance to both neoplastic and viral disease. Type I interferons (interferon a and interferon P) are produced by a number of different cell types and appear very rapidly after viral infection. Type I interferons inhibit viral replication, inhibit cell proliferation, and increase the lytic potential of NK cells and therefore play a role in controlling viral and neoplastic disease. Several cytokines are important in the initiation of inflammatory responses. Those that have received the most attention include tumor necrosis factor alpha (TNFa), interleukin (IL)-1, and IL-6. There are also a number of chemotactic cytokines (including IL-8), called chemokines, which help to mobilize immune cells to the site of injury. 

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