Consensus IFNs

Consensus IFN-a has been used in various populations of HCV-infected patients but the published results are variable. Consensus IFN-a gave a higher response rate than the combination of standard IFN-a and ribavirin in patients who relapsed... 

Hybrid and Consensus IFNs. After the sequences of all IFN-a subtypes and their activities were deduced, recombinant hybrids were designed to improve the activity of natural subtypes. It is possible to radically change the properties of an IFN by making hybrids. For example, a hybrid made from the first 61 amino-acid residues of IFN-al and the last 104 amino-acid residues of IFN-a2 exhibited high antiviral activity on mouse cells, while another hybrid produced from the first 91 amino-acid residues of IFN-al and the last 72 amino-acid residues of IFN-a4 had no antiviral effect but displayed enhanced antitumor activity in mice, a property neither of the parent molecules exhibit. Structure-function analysis of hybrid molecules has indicated that the NH2 terminus portion of the IFN-a molecule is important for its biological activity [46]. 

Consensus IFN (IFN-conl) is a synthetic nonnaturally occurring IFN-a hybrid designed by assigning each of the most frequently observed amino acids in the Hu-IFN-a subtypes. For the most part it is a... 

IFN-acon-l (consensus IFN) Infer gen (Amgen Inc.) Chronic hepatitis C... 

Repeat treatment After a repeat treatment had been decided on, increased dosage and prolonged duration of IFNa (237) or consensus IFN (160) were used. Other possible combinations were applied, such as IFNa + thymosin (236), IFNa + cyclosporin (223, 228), IFNa + UDCA (230) or IFNa + amantadine (250). In all these studies, positive results and an improvement in quality of life quality were described for some patients. Even iron removal can be used as an additional measure. (217, 243) Likewise, good results in some patients have also been achieved with immunostimulants or adjuvant sub-... 

Lymphoblastoid IFN-a also exists this is a mixture of natural IFN-a subtypes with different structures of the carbohydrate chains. Furthermore, a consensus IFN-a has been developed this is a genetically modified IFN-a, which has the properties of various IFN-a subtypes. Thus its biological activity is increased (by ca. 30% in chronic hepatitis C, probably due to better receptor affinity). 

Infergen (interferon alfacon-1 or consensus interferon) is an engineered interferon recently approved for the treatment of hepatitis C (Table 8.8). The development of infergen entailed initial sequence comparisons between a range of IFN-as. The product s amino acid sequence reflects the most frequently occurring amino acid residue in each corresponding position of these native interferons. A DNA sequence coding for the product was synthesized and inserted into E. coli. The recombinant product accumulates intracellularly as inclusion bodies. 

Infergen (interferon acon-1, or consensus interferon) is an engineered IFN recently approved for the treatment of hepatitis C (Table 4.8). The development of Infergen entailed initial... 

Consensus interferon (Con-IFN) Treatment of viral infections Rat Aerosol Tnax 25-30 min estimated bioavailability ca. 70% [101]... 

Interferons (IFN) are glycoproteins which possess antiviral, antiproliferative and immunomodulatory properties. Besides the main types a, P and y, other forms are available (lymphoblastoid IFNa, consensus IFNa). Administration is subcutaneous. Bioavailability is about 90%. The serum peak is reached by using IFNa2a after 6-8 hours with a half-life period of 5 hours or by using IFNa2b after 3-12 hours with a half-life of 3 hours. Elimination is primarily via the kidneys. Interferons inhibit CYPIA2. There is no development of resistance. (158, 160, 182) (see chapter 40.5.1.1)... 

These last factors also up-regulate hBD-2 secretion by the intestinal epithelial cell lineage Caco-2 stimulated with probiotic bacteria [176]. Although not yet demonstrated experimentally, mammalian cathelicidins may respond to inflammatory stimuli, since the 5 flanking sequences upstream of the peptide coding sequence have several potential consensus sequences for transcription factors involved in inflammatory response, sueh as NF-kB, NF-IL-6, acute-phase response factor and IFN-y response elements [147,170,177]. 

The American Association for the Study of Liver Diseases (AASLD) has published its guidelines for the management of chronic HBV. In addition, the Asian Pacific Association for the Study of the Liver (APASL) has updated a consensus statement on the management of chronic HBV. The choice of first-line therapy between IFN- 2b and lamivudine is dependent on the categorization of specific patient populations by HBeAg positivity and ALT level. As stated earlier, factors such as disease severity, history of flares, hepatic function, drug cost, side-effect profile, and patient choice ultimately drive drug selection. 

Immunomodulatory. Consensus sequence derived Interferon alpha, differs from human interferon alpha by 20 residues (88% identical to IFN alpha 2a)... 

Ozone inhalation (2 ppm, 3 h) caused a marked increase in spontaneous production of nitric oxide by type II cells (Punjabi et al. 1994). Cells from ozone-treated rats also produced significantly more nitric oxide in response to IFN-y alone and in combination with IL-ip or TNF-a than did cells from control rats. Northern blot analysis demonstrated that both increased spontaneous and IFN-y-induced production of nitric oxide by cells from ozone-exposed animals was due to an increase in inducible NOS mRNA expression. The promoter region for nitric oxide synthase gene contains consensus sequences for NfwB (). Treatment of type II pneumocytes from both control and ozone (2 ppm, 2 h) exposed rats with pyrrolidine dithiocarbamate, an inhibitor of NfxB activity, suppressed the ability of these cells to produce nitric oxide (Heck et al. 1996). 

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