Interferon inducers

W. Regelson, A. Munson, and W. Wooles, Interferon and Interferon Inducers, International Symposium Standards, London, 1969, Symposium Series Immunobi-ological Standards, S. Kager, Basel, pp. 14, 227 (1978). 

Ajami K, Pitman MR, Wilson CH et al (2008) Stromal cell-derived factors lalpha and Ibeta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8. FEBS Lett 582 819-825 Albright AV, Shieh JT, O Connor Ml et al (2000) Characterization of cultured microglia that can be infected by HIV-1. J Neurovirol 6(Suppl 1) S53-S60 Allen SJ, Crown SE, Handel TM (2007) Chemokine receptor structure, interactions, and antagonism. Annu Rev Immunol 25 787-820... 

Type I interferons induce a vims-resistant state in human cells, whereas Type II are more active in inhibiting growth of tumour cells. 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

Adverse Effects Adverse effects are common with the beta interferons (Table 26-3). Commonly, flulike symptoms consist of fever, fatigue, muscle aches, malaise, and chills. Symptoms begin a few hours after the injection and dissipate 8 to 24 hours later.38 Preventive measures can be employed (Table 26-4). In temperature-sensitive patients, beta interferon-induced fever... 

Interferon-a causes hypothyroidism in up to 39% of patients being treated for hepatitis C infection. Patients may develop a transient thyroiditis with hyperthyroidism prior to becoming hypothyroid. The hypothyroidism may be transient as well. Asians and patients with preexisting anti-TPOAbs are more likely to develop interferon-induced hypothyroidism. The mechanism of interferon-induced hypothyroidism is not known. If LT4 replacement is initiated, it should be stopped after 6 months to re-evaluate the need for replacement therapy. 

Interferon-inducible T cell alpha chemoattractant (I-TAC) Stromal cell-derived factor-1 (SDF-1)... 

Polynucleotides. Polynucleotides are potent interferon inducers. A mismatched, double-stranded synthetic polyribonucleotide ampligen and the double-stranded acids, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acids have been widely studied for cancer therapy(ii). Although these materials elicit excellent activity with murine rodents, therapeutic effects are dramatically decreased within primates. 

Chang YE et al. Microarray analysis identifies interferon-inducible genes and Stat-1 as major transcriptional targets of human papillomavims type 31. J Virol 2000 74 4174-4182. 

Interferons induce a wide range of biological effects. Generally, type I interferons induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

Not all type I interferons induce exactly the same range of responses, and the antiviral to antiproliferative activity ratio differs from one type I interferon to another. As all bind the same receptor, the molecular basis by which variation in biological activities is achieved is poorly understood as yet. 

The ability of interferons (especially type I interferons) to induce an antiviral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional interferon actions. The ability of such systems to stall protein synthesis in cells may play a role in interferon-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating interferon-induced anti-proliferative effects on various transformed cells. 

The basic structure of carboxyethylgermanium sesquioxide, a low-toxicity y-interferon inducing agent, consists of a 12-membered ring containing six Ge tetrahedra bridged by oxygen atoms. 

Effects of interferon-inducing agents on hepatic cytochrome P-450 drug metabolizing systems. Armais of the New York Academy of Sciences, 350, 314—331. 

Perussia, B., Dayton, E. T., Lazarus, R., Fanning, V., Trinchieri, G. (1983). Immune interferon induces the receptor for monomeric IgGl on human monocytic and myeloid cells. J. Exp. Med. 158,1092-113. 

Steinbeck, M. J., Webb, D. S. A., Roth, J. A. (1989). Role for arachidonic acid metabolism and protein synthesis in recombinant bovine interferon- /induced activation of bovine neutrophils. J. Leuk. Biol. 46, 450-60. 

Loeb, K. R. and Haas, A. L. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins, / Biol Chem 1992, 267, 7806-7813. 

Tissot, C. and N. Meghti, Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. J Biol Chem, 1995, 270(25), 14891-8. 

Naeasimhan, j.. Potter, J. L., and Haas, A. L. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin, J Biol Chem, 1996, 273, 324-30. 

Denovan-Wright EM, Ferrier GR, Robertson HA, Hewlett SE. 2000. Increased expression of the gene for a-interferon inducible protein in cardiomyopathic hamster heart. Bio-chem Biophys Res Comm 267 103. 

Lucas, M., Mashimo, T, Frenkiel, M. P., et al. (2003) Infection of mouse neurones by West Nile virus is modulated by the interferon-inducible 2 -5" oligoadenylate synthetase lb protein. Immunol. Cell Biol. 81, 230-236. 

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