Ingested Type I Interferon—State of the Art as Treatment for Autoimmunity Part 2
Abstract
:Introduction
Experimental Section
Results
Discussion
Conclusions
Acknowledgements
References
- Brod, S.A. Hypothesis: multiple sclerosis is a type I interferon deficiency syndrome. Proc. Soc. Exp. Biol. Med. 1998, 218, 278–283. [Google Scholar]
- Brod, S.A. Gut response. Therapy with ingested immunomodulatory proteins. Arch. Neurol. 1997, 54, 1300–1302. [Google Scholar] [PubMed]
- Tompkins, W.A. Immunomodulation and therapeutic effects of the oral use of interferon- alpha: mechanism of action [In Process Citation]. J. Interferon Cytokine Res. 1999, 19, 817–828. [Google Scholar]
- Bocci, V. Is interferon effective after oral administration? J. Biol. Reg. Homeost. Agents 1990, 4, 81–83. [Google Scholar]
- Wolinsky, J. Multiple Sclerosis. In Current Neurology; Appel, S., Ed.; Mosby - Year Book, Inc: New York, NY, USA, 1993; Volume 13, pp. 167–207. [Google Scholar]
- McFarlin, D.; McFarland, H. Multiple Sclerosis. N. Eng. J. Med. 1982, 307, 1183–1188. [Google Scholar]
- Antel, J.P.; Arnason, B.G.W.; Medof, M.E. Suppressor cell function in multiple sclerosis: correlation with clinical disease activity. Ann. Neurol. 1979, 5, 338–342. [Google Scholar]
- Group, T.I.M.S.S. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double- blind, placebo-controlled trial. Neurology 1993, 43, 655–661. [Google Scholar] [PubMed]
- Jacobs, L.; Cookfair, D.; Rudick, R.; Herndon, R.; Richert, J.; Salazar, A.; Fischer, J.; Granger, C.; Simon, J.; Goodkin, D.; Granger, C.; Simon, J.; Alam, J.; Bartoszak, D.; Bourdette, D.; Braiman, J.; Brownscheidle, C.; Coats, M.; Cohan, S.; Dougherty, D.; Kinkel, R.; Mass, M.; Munschauer, F.; Priore, R.; Pullicino, P.; Scherokman, B.; Whitham, R. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann. Neurol. 1994, 39, 285–294. [Google Scholar]
- Myhr, K.M.; Riise, T.; Green Lilleas, F.E.; Beiske, T.G.; Celius, E.G.; Edland, A.; Jensen, D.; Larsen, J.P.; Nilsen, R.; Nortvedt, M.W.; Smievoll, A.I.; Vedeler, C.; Nyland, H.I. Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis. Neurology 1999, 52, 1049–1056. [Google Scholar]
- Durelli, L.; Bongioanni, M.R.; Cavallo, R.; Ferrero, B.; Ferri, R.; Ferrio, M.F.; Bradac, G.B.; Riva, A.; Vai, S.; Geuna, M.; et al. Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis. Neurology 1994, 44, 406–413. [Google Scholar] [PubMed]
- Brex, P.A.; Gomez-Anson, B.; Parker, G.J.; Molyneux, P.D.; Miszkiel, K.A.; Barker, G.J.; MacManus, D.G.; Davie, C.A.; Plant, G.T.; Miller, D.H. Proton MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis. J. Neurol. Sci. 1999, 166, 16–22. [Google Scholar]
- Losseff, N.A.; Kingsley, D.P.; McDonald, W.I.; Miller, D.H.; Thompson, A.J. Clinical and magnetic resonance imaging predictors of disability in primary and secondary progressive multiple sclerosis. Mult. Scler. 1996, 1, 218–222. [Google Scholar]
- Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group [see comments]. Neurology 1995, 45, 1277–1285.
- Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first three years. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neurology 1996, 47, 889–894. [PubMed]
- Brod, S.A.; Marshall, G.D., Jr.; Henninger, E.M.; Sriram, S.; Khan, M.; Wolinsky, J.S. Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis. Neurology 1996, 46, 1633–1638. [Google Scholar]
- Foulis, A.K.; Liddle, C.N.; Farquharson, M.A.; Richmond, J.A.; Weir, R.S. The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia 1986, 29, 267–274. [Google Scholar]
- Silverstein, J.; Maclaren, N.; Riley, W.; Spillar, R.; Radjenovic, D.; Johnson, S. Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. N. Engl. J. Med. 1988, 319, 599–604. [Google Scholar]
- The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group [see comments]. N. Engl. J. Med. 1993, 329, 977–986. [CrossRef] [PubMed]
- Shah, S.; Malone, J.; Simpson, N. A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N. Engl. J. Med. 1989, 320, 550–554. [Google Scholar]
- Bougneres, P.; Landais, P.; Boisson, C.; Carel, J.; Frament, N.; Boitard, C.; Chaussain, J.; Bach, J. Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin. Diabetes 1990, 39, 1264–1272. [Google Scholar]
- Anonymous. Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. The Canadian-European Randomized Control Trial Group. Diabetes 1988, 37, 1574–1582. [Google Scholar] [PubMed]
- Atkison, P.R.; Mahon, J.L.; Dupre, J.; Stiller, C.R.; Jenner, M.R.; Paul, T.L.; Momah, C.I. Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: results from the Canadian open study. J. Autoimmun. 1990, 3, 793–799. [Google Scholar]
- Cook, J.; Hudson, I.; Harrison, L.; Dean, B.; Colman, P.; Werther, G.; Warne, G.; Court, J. Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes. Diabetes 1989, 38, 779–783. [Google Scholar]
- Pozzilli, P.; Visalli, N.; Boccuni, M.; Baroni, M.; Buzzetti, R.; Fioriti, E.; Signore, A.; Cavallo, M.; Andreani, D.; Lucentini, L.; et al. Combination of nicotinamide and steroid versus nicotinamide in recent-onset IDDM. The IMDIAB II Study. Diabetes Care 1994, 17, 897–900. [Google Scholar] [PubMed]
- Lewis, C.; Canafax, D.; Sprafka, J.; Barbosa, J. Double-blind randomized trial of nicotinamide on early-onset diabetes. Diabetes Care 1992, 15, 121–123. [Google Scholar]
- Koivisto, V.; Aro, A.; Cantell, K.; Haataja, M.; Huttunen, J.; Karonen, S.; Mustajoki, P.; Pelkonen, R.; Seppala, P. Remissions in newly diagnosed type 1 (insulin-dependent) diabetes: influence of interferon as an adjunct to insulin therapy. Diabetologia 1984, 27, 193–197. [Google Scholar]
- Available online: www.ClinicalTrials.gov accessed on 13 April 2010, Trial Identifier NCT00100178.
- Available online: www.ClinicalTrials.gov accessed on 13 April 2010, Trial Identifier NCT00279205.
- Keymeulen, B.; Vandemeulebroucke, E.; Ziegler, A.G.; Mathieu, C.; Kaufman, L.; Hale, G.; Gorus, F.; Goldman, M.; Walter, M.; Candon, S.; Schandene, L.; Crenier, L.; De Block, C.; Seigneurin, J.M.; De Pauw, P.; Pierard, D.; Weets, I.; Rebello, P.; Bird, P.; Berrie, E.; Frewin, M.; Waldmann, H.; Bach, J.F.; Pipeleers, D.; Chatenoud, L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N. Engl. J. Med. 2005, 352, 2598–2608. [Google Scholar]
- Herold, K.C.; Gitelman, S.E.; Masharani, U.; Hagopian, W.; Bisikirska, B.; Donaldson, D.; Rother, K.; Diamond, B.; Harlan, D.M.; Bluestone, J.A. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 2005, 54, 1763–1769. [Google Scholar]
- Haller, M.J.; Gottlieb, P.A.; Schatz, D.A. Type 1 diabetes intervention trials 2007: where are we and where are we going? Curr. Opin. Endocrinol. Diabetes Obes. 2007, 14, 283–287. [Google Scholar] [CrossRef] [PubMed]
- Ludvigsson, J.; Faresjo, M.; Hjorth, M.; Axelsson, S.; Cheramy, M.; Pihl, M.; Vaarala, O.; Forsander, G.; Ivarsson, S.; Johansson, C.; Lindh, A.; Nilsson, N.O.; Aman, J.; Ortqvist, E.; Zerhouni, P.; Casas, R. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N. Engl. J. Med. 2008, 359, 1909–1920. [Google Scholar]
- Isaacs, A.; Lindenmann, J. Virus Interference I. The interferon. Proc. R. Soc. Lond. [Biol.] 1957, 147, 258–267. [Google Scholar] [CrossRef]
- Dron, M.; Tovey, M. Interferon alpha/beta, gene structure and regulation. In Interferon: Principles and Medical Applications; Baron, S., Coppenhaver, D.H., Dianzani, F., Fleischmann, W.R., Hughes, T.K., Klimpel, G.R., Niesel, D.W., Stanton, G.J., Tyring, S.K., Eds.; UT Press: Galveston, TX, USA, 1992; pp. 33–45. [Google Scholar]
- Johnson, H.M.; Baron, S. Evaluation of the effects of interferon and interferon inducers on the immune response. Pharm. Ther. 1977, 1, 349–367. [Google Scholar]
- Zoon, K.C. Human Interferons: Structure and Function. In Interferon 9; Academic Press: London, UK, 1987; Volume 9, pp. 1–12. [Google Scholar]
- Rashidbaigi, A.; Pestka, S. Interferons: Protein Structure. In Interferon System; Baron, S., Dianzani, F., Stanton, G.J., Fleischmann, W.R., Eds.; UT Press: Austin, TX, USA, 1987; pp. 149–168. [Google Scholar]
- Uze, G.; Lutfalla, G.; Knudson, K.E. α and β Interferons and their receptor and their friends and relations. J. Interferon Cyt. Res. 1995, 15, 3–26. [Google Scholar] [CrossRef]
- Aguet, M.; Mogensen, K.E. Interferon Receptors. In Interferons; Gresser, I., Ed.; Academic Press: New York, NY, USA, 1983; Volume 5, pp. 1–22. [Google Scholar]
- Rollwagen, R.; Baqar, S. Oral cytokine administration. Immunol. Today 1996, 17, 548–550. [Google Scholar]
- Witt, P.J.; Goldstein, D.; Storer, B.E.; Grossberg, S.E.; Flashner, M.; Colby, C.B.; Borden, E.C. Absense of biological effects of orally administered interferon-βser. J. Interferon Res. 1992, 12, 411–413. [Google Scholar]
- Bocci, V. Absorption of cytokines via the oropharyngeal associated lymphoid tissues - Does an unorthodox route improve the therapeutic index of interferon. Clin. Pharmacokinet 1991, 21, 411–417. [Google Scholar] [CrossRef] [PubMed]
- Brandtzaeg, P. Overview of the mucosal immune system. Curr. Topics Microbiol. Immunol. 1989, 146, 13–28. [Google Scholar]
- MacDonald, T.T. Immunosuppression caused by antigen feeding II. Suppressor T cells mask Peyer's patch B cell priming to orally administered antigen. Eur. J. Immunol. 1983, 13, 138–142. [Google Scholar] [CrossRef] [PubMed]
- Mattingly, J.A. Immunologic suppression after oral administration of antigen. III. Activation of suppressor-inducer cells in the Peyer's patches. Cell Immunol. 1984, 86, 46–52. [Google Scholar] [CrossRef] [PubMed]
- Pfeffer, L.M.; Donner, D.D. The downregulation of IFN-α receptors in human lymphoblastoid cells: relation of cellular responsiveness to antiproliferative action of IFN-α. Cancer Res. 1990, 50, 2654–2657. [Google Scholar]
- Pfeffer, L.M.; Colamonici, O.R. Transmembrane signalling by interferon-α. Pharmac.Ther. 1991, 52, 149–151. [Google Scholar]
- Baron, S.; Coppenhaver, D.H.; Dianzani, F.; Fleischmann, W.R.; Hughes, T.K.; Klimpel, G.R.; Niesel, D.W.; Stanton, G.J.; Tyring, S.K. Introduction to the interferon system. In Interferon: Principles and Medical Applications; Baron, S., Coppenhaver, D.H., Dianzani, F., Fleischmann, W.R., Hughes, T.K., Klimpel, G.R., Niesel, D.W., Stanton, G.J., Tyring, S.K., Eds.; UT-Galveston: Galveston, TX, USA, 1992; pp. 1–15. [Google Scholar]
- Fleischmann, W.R., Jr.; Koren, S.; Fleischmann, C.M. Orally administered interferons exert their white blood cell suppressive effects via a novel mechanism. Proc. Soc. Exp. Biol. Med. 1992, 201, 200–207. [Google Scholar]
- Cantell, K.; Pyhala, L. Circulating interferon in rabbits after administration of human interferon by different routes. J. Gen. Virol. 1973, 20, 97–104. [Google Scholar]
- Gibson, D.M.; Cotler, S.; Spiegel, H.E.; Colburn, W.A. Pharmacokinetics of recombinant leukocyte A interferon following various routes and modes of administration to the dog. J. Interferon Res. 1985, 5, 403–408. [Google Scholar]
- Wills, R.J.; Spiegel, H.E.; Soike, K.F. Pharmacokinetics of recombinant alpha A interferon following I.V. infusion and bolus, I.M., and P.O. administrations to African green monkeys. J. Interferon Res. 1984, 4, 399–409. [Google Scholar] [CrossRef] [PubMed]
- Horisberger, M.A. Mx protein: Function and mechanism of action. In Interferon: Principles and Medical Applications; Baron, S., Coppenhaver, D.H., Dianzani, F., Fleischmann, W.R., Hughes, T.K., Klimpel, G.R., Niesel, D.W., Stanton, G.J., Tyring, S.K., Eds.; UT Press: Galveston, TX, USA, 1992; pp. 215–224. [Google Scholar]
- Roers, A.; Hochkeppel, H.; Horisberger, M.; Hovanessian, A.; Haller, O. MxA gene expression after live virus vaccination: A sensitive marker for endogenous type I interferon. J. Infect. Dis. 1994, 169, 807–813. [Google Scholar]
- Brod, S.A.; Khan, M. Oral administration of IFN-alpha is superior to subcutaneous administration of IFN-alpha in the suppression of chronic relapsing experimental autoimmune encephalomyelitis. J. Autoimmun. 1996, 9, 11–20. [Google Scholar]
- Brod, S.A.; Nelson, L.; Jin, R.; Wolinsky, J.S. Ingested interferon alpha induces Mx mRNA. Cytokine 1999, 11, 492–499. [Google Scholar]
- Brod, S.A.; Khan, M.; Bright, J.; Sriram, S.; Marshall, G.D., Jr.; Henninger, E.M.; Kerman, R.H.; Wolinsky, J.S. Decreased CD3-mediated interferon-gamma production in relapsing- remitting multiple sclerosis. Ann. Neurol. 1995, 37, 546–549. [Google Scholar]
- Brod, S.A.; Khan, M.; Nelson, L.D.; Decuir, B.; Malone, M.; Henninger, E. Adoptive transfer from interferon-alpha-fed mice is associated with inhibition of active experimental autoimmune encephalomyelitis by decreasing recipient tumor necrosis factor-alpha secretion. J. Immunother. 2000, 23, 235–245. [Google Scholar]
- Brod, S.A.; Scott, M.; Burns, D.K.; Phillips, J.T. Modification of acute experimental autoimmune encephalomyelitis in the Lewis rat by oral administration of type 1 interferons. J. Interferon Cytokine Res. 1995, 15, 115–122. [Google Scholar]
- Brassard, D.L.; Grace, M.J.; Bordens, R.W. Interferon-alpha as an immunotherapeutic protein. J. Leukoc. Biol. 2002, 71, 565–581. [Google Scholar]
- Xing, T.; Zhang, L.; Lu, Q.; Hou, J.; Feng, X.; Luo, K. Th1/Th2 type cytokines in hepatitis B patients treated with interferon-alpha. Chin. Med. J. (Engl.) 2001, 114, 921–924. [Google Scholar] [PubMed]
- Monteleone, G.; Pender, S.L.; Wathen, N.C.; MacDonald, T.T. Interferon-alpha drives T cell-mediated immunopathology in the intestine. Eur. J. Immunol. 2001, 31, 2247–2255. [Google Scholar]
- Brod, S.A.; Kerman, R.H.; Nelson, L.D.; Marshall, G.D., Jr.; Henninger, E.M.; Khan, M.; Jin, R.; Wolinsky, J.S. Ingested IFN-alpha has biological effects in humans with relapsing- remitting multiple sclerosis. Mult. Scler. 1997, 3, 1–7. [Google Scholar]
- Isaac, C.; Li, K.B.; Genton, M.; Jardine, C.; Grochowski, E.; Palmer, M.; Kastruloff, L.F.; Oger, J.J.; Paty, D.W. MS: A serial study using MRI in relapsing patients. Neurology 1988, 38, 1511–1515. [Google Scholar]
- Miller, D.H.; Barkhof, F.; Berry, I.; Kappos, L.; Scotti, G.; Thompson, A.J. MR imaging in monitoring the treatment of multiple sclerosis: Concerted action guidelines. J. Neurol. Neurosurg. Psychiat. 1991, 54, 683–688. [Google Scholar]
- Paty, D.W.; Oger, J.J.; Kastruloff, L.F.; Hashimoto, S.A.; Hooge, J.J.; Eisen, A.A.; Eisen, K.A.; Purves, S.J.; Low, M.; Brangjes, V.; Robertson, W.; Li, D.B.K. Biologic vs. clinical MS. Neurology 1989, 39, 151–153. [Google Scholar] [PubMed]
- Thompson, A.J.; Kermode, A.J.; MacManus, D.G.; Kendall, B.E.; Kingsley, D.P.E.; Moseley, I.F.; McDonald, W.I. Patterns of disease activity in MS: clinical and MRI study. Br. Med. J. 1990, 300, 631–634. [Google Scholar]
- Thompson, A.J.; Miller, D.; Youl, B.; MacManus, D.; Moore, S.; Kingsley, D.P.E.; Kendall, B.E.; Feinstein, A.; McDonald, W.I. Serial gadolinium enhanced MRI in RR MS of varying didease duration. Neurology 1993, 42, 60–63. [Google Scholar]
- Willoughby, E.W.; Grochowski, E.; Li, D.K.; Oger, J.; Kastrukoff, L.F.; Paty, D.W. Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. Ann. Neurol. 1989, 25, 43–49. [Google Scholar]
- Brod, S.; Orlander, P.; Lavis, V.; Brosnan, P.; Hardin, D.; Henninger, E.; Nyugen, M.; Riley, W. Ingested IFN-α prolongs the “honeymoon” period in newly diagnosed type I diabetes mellitus. J. Interferon Cytokine Res. 2001, 21, 1021–1030. [Google Scholar]
- Calabrese, E.J. Hormetic dose-response relationships in immunology: occurrence, quantitative features of the dose response, mechanistic foundations, and clinical implications. Crit. Rev. Toxicol. 2005, 35, 89–295. [Google Scholar] [CrossRef] [PubMed]
- Brod, S.A.; Nguyen, M.; Hood, Z.; Shipley, G.L. Ingested (oral) IFN-alpha represses TNF-alpha mRNA in relapsing-remitting multiple sclerosis. J. Interferon Cytokine Res. 2006, 26, 150–155. [Google Scholar]
- Brod, S.; Darcan, S.; Malone, M.; Pappolla, M.; Nelson, L. Ingested IFN-α suppresses IDDM in the NOD mouse. Diabetologia 1998, 41, 1227–1232. [Google Scholar]
- Brod, S.A.; Katz, S.; Phan, T.; Stepkowski, S. Ingested interferon-alpha prevents allograft islet transplant rejection. Transplantation 2000, 69, 2162–2166. [Google Scholar]
- Daynes, R.A.; Araneo, B.A.; Dowell, T.A.; Huang, K.; Dudley, D. Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function. J. Exp. Med. 1990, 171, 979–996. [Google Scholar] [PubMed]
- Bocci, V. Roles of interferon produced in physiological conditions. A speculative review. Immunology 1988, 64, 1–9. [Google Scholar] [PubMed]
- Shiozawa, S.; Tanaka, Y.; Shiozawa, K. Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjogren's syndrome. J. Interferon Cytokine Res. 1998, 18, 255–262. [Google Scholar]
- Ship, J.A.; Fox, P.C.; Michalek, J.E.; Cummins, M.J.; Richards, A.B. Treatment of primary Sjogren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group. J. Interferon Cytokine Res. 1999, 19, 943–951. [Google Scholar] [CrossRef] [PubMed]
- Bosio, E.; Beilharz, M.W.; Watson, M.W.; Lawson, C.M. Efficacy of low-dose oral use of type I interferon in cytomegalovirus infections in vivo. J. Interferon Cytokine Res. 1999, 19, 869–876. [Google Scholar] [CrossRef] [PubMed]
- Satoh, Y.; Kasama, K.; Kuwabara, M.; Yimin; Diao, H.Y.; Nakajima, H.; Kohanawa, M.; Minagawa, T. Suppression of late asthmatic response by low-dose oral administration of interferon-beta in the guinea pig model of asthma. J. Interferon Cytokine Res. 1999, 19, 887–894. [Google Scholar] [CrossRef] [PubMed]
- Slaton, J.W.; Perrotte, P.; Inoue, K.; Dinney, C.P.; Fidler, I.J. Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin. Cancer Res. 1999, 5, 2726–2734. [Google Scholar]
- Ozawa, S.; Shinohara, H.; Kanayama, H.O.; Bruns, C.J.; Bucana, C.D.; Ellis, L.M.; Davis, D.W.; Fidler, I.J. Suppression of angiogenesis and therapy of human colon cancer liver metastasis by systemic administration of interferon-alpha. Neoplasia 2001, 3, 154–164. [Google Scholar]
- Solorzano, C.C.; Hwang, R.; Baker, C.H.; Bucana, C.D.; Pisters, P.W.; Evans, D.B.; Killion, J.J.; Fidler, I.J. Administration of optimal biological dose and schedule of interferon alpha combined with gemcitabine induces apoptosis in tumor-associated endothelial cells and reduces growth of human pancreatic carcinoma implanted orthotopically in nude mice. Clin. Cancer Res. 2003, 9, 1858–1867. [Google Scholar]
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Brod, S.A. Ingested Type I Interferon—State of the Art as Treatment for Autoimmunity Part 2. Pharmaceuticals 2010, 3, 1108-1121. https://doi.org/10.3390/ph3041108
Brod SA. Ingested Type I Interferon—State of the Art as Treatment for Autoimmunity Part 2. Pharmaceuticals. 2010; 3(4):1108-1121. https://doi.org/10.3390/ph3041108
Chicago/Turabian StyleBrod, Staley A. 2010. "Ingested Type I Interferon—State of the Art as Treatment for Autoimmunity Part 2" Pharmaceuticals 3, no. 4: 1108-1121. https://doi.org/10.3390/ph3041108