Use of oromucosally administered interferon-alpha in the prevention and treatment of animal diseases

• Autorzy: Dec M. , Puchalski A.
• Języki publikacji: EN

Abstrakty

EN

Interferon-a (IFN-a) is well known as a clinically effective antiviral and antineoplastic therapeutic agent. It has also been shown to have immunoregulatory properties. IFN-a stimulates a cell-mediated innate immune response and then participates in the transition of the initial host innate response to an effective adaptive immune response. IFN-a is produced in small quantities in nasal secretions during viral infections, prompting many authors to suggest that low-dose oromucosal administration of IFN-a effectively mimics nature. Moreover, the injectable high-dose interferon therapy currently approved for various human disorders causes numerous side effects. By contrast, oromucosal administration of IFN-a is not associated with toxic effects. Another distinct advantage is ease of administration: the IFN can be dissolved in drinking water or administered by nebulization to the oral or nasal cavity. This review describes the current state of knowledge concerning orally administered IFN-a, of both human and animal origin, as a prophylactic or therapeutic agent in veterinary medicine. We present the effects of IFN-a in such animals as cattle, pigs, horses, cats, dogs and chickens, and attempt to explain its mechanism of action following oromucosal administration. It is hoped that this review of the medical literature on the use of IFN-a in animals will give practitioners a better understanding of the challenges and benefits of using this interesting cytokine in clinical practice.

Słowa kluczowe

EN

interferon alpha; animal disease; prevention; treatment; oral administration; immunoregulatory property

• Wydawca: -
• Czasopismo: Polish Journal of Veterinary Sciences
• Rocznik: 2008
• Tom: 11
• Numer: 2
• Opis fizyczny: p.175-186,fig.,ref.

Twórcy

autor

Dec M.

• University of Life Sciences, Akademicka 12, 20-033 Lublin, Poland

autor

Puchalski A.

Bibliografia

• Ambrosio D, Piscopo L, Lauro C, Rotondi M, Gallo E, Balbi F (2001) Treatment of ovarian carcinoma with intraperitoneal administration of interferon alpha 2b.Minerva Ginecol 53 (1 Suppl 1): 67-71.
• Antonelli G, Currenti M, Turriziani O, Dianzani F 11991 Neutralizing antibodies to interferon-alpha: relative fre­quency in patients treated with different interferon prep­arations. J Infect Dis 163: 882-885
• Babiuk LA, Ohmann HB, Gifford G, Czarniecki CW, Scialli VT, Hamilton EB (1985) Effect of bovine alpha 1 inter­feron on bovine herpesvirus type 1-induced respiratory disease. J Gen Virol 66: 2383-2394.
• Baldwin SL, Powell TD, Sellins KS, Radecki SV, John Co­hen J, Milhausen MJ (2004) The biological effects of five feline IFN-alpha subtypes. Vet Immunol Immunopathol 99: 153-167
• Balkwill F, Taylor-Papadimitriou J (1978) Interferon affects both G1 and S + G2 in cells stimulated from quiescence to growth. Nature 274: 798-800.
• Beilharz MW, Cummins JM, Bennett AL (2007) Protection from lethal influenza virus challenge by oral type 1 inter­feron. Biochem Biophys Res Commun 355: 740-744.
• Beilharz MW, McDonald W, Watson MW, Heng J, McGeachie J, Lawson CM (1997) Low-dose oral type I interferons reduce early virus replication of murine cytomegalovirus in vivo. J Interferon Cytokine Res 17: 625-630.
• Begni B, Amadori M, Ritelli M, Podavini D (2005) Effects of IFN-alpha on the inflammatory response of swine leukocytes to bacterial endotoxin. J Interferon Cytokine Res 25: 202-208.
• Bocci V (1981) Production and role of interferon in physio­logical conditions Biol Rev Camb Philos Soc 56, 49-85.
• Brassard DL, Grace MJ, Bordens RW (2002) Interferon-a as an immunotherapeutic protein. J Leukoc Biol 71: 565-581.
• Bridgman R, Rossi CR, Campos M (1988) The sensitivity of domestic animal cell lines to eight recombinant human interferons. J Interferon Res 8: 1-4.
• Capon DJ, Shepard HM, Goeddel DV (1985) Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypept­ides. Mol Cell Biol 5: 768-779.
• Chambers PJ, Saltis J, Alin P, Wright A, Linnane AW, Chee- tham BF (1990) Receptors for human interferon alpha on bovine cells: specificity and tissue distribution. Im- munopharmacol Immunotoxicol 12: 513-525.
• Chaplin PJ, Parsons KR, Collins RA (1996) The cloning of cattle interferon-a subtypes isolated from the gut epi­thelium of rotavirus-infected calves. Immunogenetics 44: 143-145.
• Cheng G, Chen W, Li Z, Yan W, Zhao X, Xie J, Liu M, Zhang H, Zhong Y, Zheng Z (2006) Characterization of the porcine alpha interferon multigene family. Gene 382: 28-38.
• Cocker FM, Newby TJ, Gaskell RM, Evans PA, Gaskell CJ, Stokes CR, Harbour DA, Bourne JF (1986) Responses of cats to nasal vaccination with a live, modified feline herpesvirus type 1. Res Vet Sci 41: 323-330.
• Corssmit EP, de Metz J, Sauerwein HP, Romijn JA (2000) Biologic responses to IFN-a administration in humans. J Interferon Cytokine Res 20: 1039-1047.
• Cremer B, Kohlmus C, Czarnetzki BM (1995) Topical inter­feron alpha in atopic eczema J Eur Acad Dermatol Ve- nereol 5: 153-156.
• Cummins JM, Tompkins MB, Olsen RG, Tompkins WA, Lewis MG (1988) Oral use of human alpha interferon in cats. J Biol Response Mod 7: 513-523.
• Cummins JM, Hutcheson DP, Cummins MJ, Georgiades JA, Richards AB (1993a) Oral therapy with human inter­feron alpha in calves experimentally injected with infec­tious bovine rhinotracheitis virus. Arch Immunol Ther Exp (Warsz) 41: 193-197.
• Cummins JM, Gawthrop J, Hutcheson DP, Cummins MJ, Zeck D (1993b) The effect of low dose oral human inter­feron alpha therapy on diarrhea in veal calves. Arch Im­munol Ther Exp (Warsz) 41: 199-203.
• Cummins JM, Georgiades JA (1993) How it began. Arch Immunol Ther Exp (Warsz) 41: 169-172.
• Cummins JM, Mock RE, Shive BW, Krakowka S, Richards AB, Hutcheson DP (1995) Oral treatment of transmiss­ible gastroenteritis with natural human interferon alpha: a field study. Vet Immunol Immunopathol 45: 355-360.
• Cummins JM, Beilharz MW, Krakowka S (1999a) Oral use of interferon. J Interferon Cytokine Res 19: 853-857.
• Cummins JM, Guthrie D, Hutcheson DP, Krakowka S, Rosenquist BD (1999b) Natural human interferon-alpha administered orally as a treatment of bovine respiratory disease complex. J Interferon Cytokine Res 19: 907-910.
• Cummins MJ, Pruitt B (1999) Low-dose oral use of human interferon-alpha in cancer patients. J Interferon Cytokine Res 19: 937-941.
• Cummins JM, Krakowka GS, Thompson CG (2005) Sys­temic effects of interferons after oral administration in animals and humans. Am J Vet Res 66:164-176.
• Dao T, Takeuchi M, Fukuda S, Kurimoto M (1995) Natural human interferon-alpha enhances the expression of in­tracellular adhesion molecule-1, integrin alpha 2 and beta 1 by a mucosal epithelial cell line. Folia Biol (Praha) 41: 213-225.
• D’Cunha J, Knight E Jr, Haas AL, Truitt RL, Borden EC (1996) Immunoregulatory properties of ISG15, an inter­feron-induced cytokine. Proc Natl Acad Sci USA 93: 211-215.
• Devitt A, Lund PA, Morris AG, Pearce JH (1996) Induction of alpha/beta interferon and dependent nitric oxide syn­thesis during Chlamydia trachomatis infection of McCoy cells in the absence of exogenous cytokine. Infect Immun 64: 3951-3956.
• Dhingra K, Duvic M, Hymes S, McLaughlin P, Rothberg J, Gutterman JU (1993) A phase-I clinical study of low-dose oral interferon-alpha. J Immunother Emphasis Tumor Immunol 14: 51-55.
• Diez B, Galdeano A, Nicolas R, Cisterna R (1989) Relation­ship between the production of interferon-alpha/beta and interferon-gamma during acute toxoplasmosis Parasitol­ogy 99: 11-15.
• Eid P, Meritet JF, Maury C, Lasfar A, Weill D, Tovey MG (1999) Oromucosal interferon therapy: pharmacokinetics and pharmacodynamics. J Interferon Cytokine Res 19: 157-169.
• Fleischmann WR Jr, Koren S, Fleischmann CM (1992) Orally administered interferons exert their white blood cell suppressive effects via a novel mechanism. Proc Soc Exp Biol Med 201: 200-207.
• Fleischmann WR Jr, Koren S (1999) Systemic effects of orally administered interferons and interleukin-2. J Inter­feron Cytokine Res 19: 829-839.
• Fleischmann WR Jr, Masoor J, Wu TY, Fleischmann CM (1998) Orally administered IFN-alpha acts alone and in synergistic combination with intraperitoneally adminis­tered IFN-gamma to exert an antitumor effect against B16 melanoma in mice. J Interferon Cytokine Res 18: 17-20.
• Fukuda A, Kobayashi H, Teramura K, Yoshimoto S, Ohsawa N (2000) Effects of interferon-alpha on peripheral neu­trophil counts and serum granulocyte colony-stimulating factor levels in chronic hepatitis C patients. Cytokines Cell Mol Ther 6: 149-154.
• Fulton RW, Burge U, McCraken JS (1986) Effect of recom­binant DNA-derived bovine and human interferons on replication of bovine herpesvirus-1, parainfluenza-3, and respiratory syncytial viruses. Am J Vet Res 47: 751-753.
• Fulton RW, Teeter RG, Cummins JM, Georgiades JA, Hutcheson DP (1993) The use of interferon modulates the negative effects of heat stress on poultry production. Arch Immunol Ther Exp (Warsz) 41: 209-212.
• Gary-Gouy H, Lebon P, Dalloul AH (2002) Type I inter­feron production by plasmacytoid dendritic cells and monocytes is triggered by viruses, but the level of produc­tion is controlled by distinct cytokines. J Interferon Cytokine Res 22: 653-659.
• Georgiades JA (1993) Effect of low dose natural human interferon alpha given into the oral cavity on the recovery time and death loss in feedlot hospital pen cattle: a field study. Arch Immunol Ther Exp (Warsz) 41: 205-207.
• Gilger BC, Rose PD, Davidson MG, Roberts SM, Miller T (1999) Low-dose oral administration of interferon-al­pha for the treatment of immune-mediated keratocon­junctivitis sicca in dogs. J Interferon Cytokine Res 19: 901-905.
• Gillespie JH, Robson DS, Scott FW, Schiff El (1985) In vitro protective effect of bacteria-derived bovine alpha interferon II against selected bovine viruses. J Clin Microbiol 22: 912-914.
• Glue P, Fang JW, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, Jacobs S (2000) Pegylated inter- feron-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Inter­vention Therapy Group. Clin Pharmacol Ther 68: 556-567.
• Goodbourn S, Didcock L, Randall RE (2000) Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81: 2341-2364.
• Hall CB, Douglas RG Jr, Simons RL, Geiman JM (1978) Interferon production in children with respiratory syn­cytial, influenza, and parainfluenza virus infections. J Pediatr 93: 28-32.
• Hailoran PF, Urmson J, Van der Meide PH, Autenried P (1989) Regulation of MHC expression in vivo. II. IFN-alpha/beta inducers and recombinant IFN-alpha modulate MHC antigen expression in mouse tissues. J Immunol 142: 4241-4247.
• Himmler A, Hauptmann R, Adolf GR, Swetly P (1986) Mol­ecular cloning and expression in Escherichia coli of equine type I interferons. DNA 5: 345-356.
• Jarosinski KW, Jia W, Sekellick MJ, Marcus PI, Schat KA (2001) Cellular responses in chickens treated with IFN-alpha orally or inoculated with recombinant Marek’s disease virus expressing IFN-alpha. J Interferon Cytokine Res 21: 287-296.
• Jordan LT, Derbyshire JB (1994) Antiviral activity of inter­feron against transmissible gastroenteritis virus in cell culture and ligated intestinal segments in neonatal pigs. Vet Microbiol 38: 263-276.
• ordan LT, Derbyshire JB (1995) Antiviral action of inter­feron-alpha against porcine transmissible gastroenteritis virus. Vet Microbiol 45: 59-70.
• Kaiser L. Fritz RS, Straus SE, Gubareva L, Hayden FG (2001) Symptom pathogenesis during acute influenza: Interleukin-6 and other cytokine responses. J Med Virol 64: 262-268.
• Khan NU, Pulford KA, Farquharson MA, Howatson A, Stewart C, Jackson R, McNicol AM, Foulis AK (1989) The distribution of immunoreactive interferon-alpha in normal human tissues. Immunology 66: 201-206.
• Kumar S, Mitnik C, Valente G, Floyd-Smith G (2000) Ex­pansion and molecular evolution of the interferon-in­duced 2’-5’ oligoadenylate synthetase gene family. Mol Biol Evol 17: 738-750.
• Lecce JG, Cummins JM, Richards AB (1990) Treatment of rotavirus infection in neonate and weanling pigs using natural human interferon alpha. Mol Biother 2: 211-216.
• Marcus PI, van der Heide L, Sekellick MJ (1999) Interferon action on avian viruses. I. Oral administration of chicken interferon-alpha ameliorates Newcastle disease. J Inter­feron Cytokine Res 19: 881-885.
• McCaw DL, Boon GD, Jergens AE, Kern MR, Bowles MH, Johnson JC (2001) Immunomodulation therapy for fe­line leukemia virus infection. J Am Anim Hosp Assoc 37: 356-363.
• Meritet JF, Maury C, Tovey MG (2001) Effect of oro- mucosal administration of IFN-alpha on allergic sensitiz­ation and the hypersensitive inflammatory response in animals sensitized to ragweed pollen. J Interferon Cytokine Res 21: 583-593.
• Moore BR (1996) Clinical application of interferons in large animal medicine. J Am Vet Med Assoc 208: 1711-1715.
• Moore BR, Krakowka S, Cummins JM, Robertson JT (1996) Changes in airway inflammatory cell populations in standardbred racehorses after interferon-alpha admin­istration. Vet Immunol Immunopathol 49: 347-358.
• Moore BR, Krakowka S, Mcvey DS, Cummins JM, Rober­tson JT (1997) Inflammatory markers in bronchoalveolar lavage fluid of standardbred racehorses with inflamma­tory airway disease: response to interferon-alpha. Equine Vet J 29: 142-147.
• Moore I, Horney B, Day K, Lofstedt J, Cribb AE (2004) Treatment of inflammatory airway disease in young stan- dardbreds with interferon alpha. Can Vet J 45: 594-601.
• Mughini L (2000) Effects of interferon alpha administered by peroral route on lymphomonocytes’ subpopulations of peripheral blood in healthy volunteers. Clin Ter 151(1 Suppl 1): 3-12.
• Murata M, Nabeshima S, Kikuchi K, Yamaji K, Furusyo N, Hayashi J (2006) A comparison of the antitumor effects of interferon-alpha and beta on human hepatocellular carcinoma cell lines. Cytokine 33: 121-128.
• Nakayama T, Urano T, Osano M, Maehara N, Makino S (1986) Alpha interferon in the sera of patients infected with Mycoplasma pneumoniae. J Infect Dis 154: 904-906.
• Namangala B. Inoue N, Kohara J, Kuboki N, Sakurai T, Hayashida K, Sugimoto C (2006) Evidence or the im- munostimulatory effects of low-dose orally delivered hu­man IFN-alpha in cattle. J Interferon Cytokine Res 26: 675-681.
• Nyman TA, Tolo H, Parkkinen J, Kalkkinen N (1998) Identification of nine interferon-alpha subtypes produced by Sendai virus-induced human peripheral blood leuco­cytes. Biochem J 329: 295-302.
• Ohtsuka H, Tokita M, Takahashi K, Masui M, Kohiruimaki M, Hayashi T, Ando T, Watanabe D, Kawamura S (2006) Peripheral mononuclear cell response in Ja­panese black calves after oral administration of IFN-al­pha. J Vet Med Sci 68: 1063-1067.
• Ohya K, Matsumura T, Itchoda N, Ohashi K, Onuma M, Sugimoto C (2005) Ability of orally administered IFN-alpha-containing transgenic potato extracts to in­hibit Listeria monocytogenes infection. J Interferon Cytokine Res 25: 459-466.
• Orinda GO, Wright IG, Leatch G, Young AS (1993) Human interferon alpha fails to inhibit the development of Babesia bigemina and Anaplasma marginale infections in cattle. Vet Parasitol 47: 149-155.
• Pedretti E, Passeri B, Amadori M, Isola P, Di Pede P, Telera A, Vescovini R, Quintavalla F, Pistello M (2006) Low-dose interferon-alpha treatment for feline im­munodeficiency virus infection. Vet Immunol Im­munopathol 109: 245-254.
• Peek SF, Bonds MD, Gangemi DG, Thomas CB, Schultz RD (2004) Evaluation of cytotoxicity and antiviral activ­ity of recombinant human interferon alfa-2a and recom­binant human interferon alfa-B/D hybrid against bovine viral diarrhea virus, infectious bovine rhinotracheitis vi­rus, and vesicular stomatitis virus in vitro. Am J Vet Res 65: 871-874
• Pei J, Sekellick MJ, Marcus PI, Choi IS, Collisson EW (2001) Chicken interferon type I inhibits infectious bron­chitis virus replication and associated respiratory illness. J Interferon Cytokine Res 21: 1071-1077.
• Pol JM, Broekhuysen-Davies JM, Wagenaar F, La Bonnar- dicre C (1991) The influence of porcine recombinant in­terferon-alpha 1 on pseudorabies virus infection of por­cine nasal mucosa in vitro. J Gen Virol 72: 933-938.
• Radwanski E, Perentesis G, Jacobs S, Oden E, Affrime M, Symchowicz S, Zampaglione N (1987) Pharmacokinetics of interferon alpha-2b in healthy volunteers. J Clin Phar­macol 27: 432-435.
• Randall RE, Goodbourn S (2008) Interferons and viruses: an interplay between induction, signalling, antiviral re­sponses and virus countermeasures. J Gen Virol 89: 1-47.
• Rhodes J, Ivanyi J, Cozens P (1986) Antigen presentation by human monocytes: effects of modifying major histocom­patibility complex class II antigen expression and inter­leukin 1 production by using recombinant interferons and corticosteroids. Eur J Immunol 16: 370-375.
• Riffault S, Carrat C, van Reeth K, Pensaert M, Charley B (2001) Interferon-alpha-producing cells are localized in gut-associated lymphoid tissues in transmissible gastro­enteritis virus (TGEV) infected piglets. Vet Res 32: 71-79.
• Roney CS, Rossi CR, Smith PC, Lauerman LC, Spano JS, Hanrahan LA, William JC (1985) Effect of human leukocyte A interferon on prevention of infectious bovine rhinotracheitis virus infection of cattle. Am J Vet Res 46: 1251-1255.
• Russell IJ, Michalek JE, Kang YK, Richards AB (1999) Re­duction of morning stiffness and improvement in physical function in fibromyalgia syndrome patients treated sub­lingually with low doses of human interferon-alpha. J In­terferon Cytokine Res 19: 961-968.
• Sandmeyer LS, Keller CB, Bienzle D (2005) Effects of inter­feron-alpha on cytopathic changes and titers for feline herpesvirus-1 in primary cultures of feline corneal epi­thelial cells. Am J Vet Res 66: 210-216.
• Seahorn TL, Carter GK, Martens JG, Crandell RA, Martin MT, Scrutchfield WL, Cummins JM, Martens RJ (1990) Effects of human alpha interferon on experimentally in­duced equine herpesvirus-1 infection in horses. Am J Vet Res 51: 2006-2010.
• Sentsui H, Takami R, Nishimori T. Murakami K, Yokoyama T, Yokomizo Y (1998) Anti-viral effect of interferon-al­pha on bovine viral diarrhea virus. J Vet Med Sci 60: 1329-1333.
• Shigeto Y, Hirohisa Y, Osamu S , Hakuo I, Masashi K, Masamichi K (2002) Different antiviral activities of IFN-h subtypes in human liver cell lines: synergism be­tween IFN-h2 and IFN-h8. Hepatol Res 24: 99-106.
• Siebeck N, Hurley DJ, Garcia M, Greene CE, Kostlin RG, Moore PA, Dietrich UM (2006) Effects of human rec­ombinant alpha-2b interferon and feline recombinant omega interferon on in vitro replication of feline herpes­virus-1. Am J Vet Res 67: 1406-1411.
• Smirnova NP, Bielefeldt-Ohmann H, Van Campen H, Aus­tin KJ, Han H, Montgomery DL, Shoemaker ML, van Olphen AL, Hansen TR (2007) Acute non-cytopathic bovine viral diarrhea virus infection induces pronounced type I interferon response in pregnant cows and fetuses. Virus Res 27: 1-10.
• Smith JK, Chi DS, Krishnaswamy G, Srikanth S, Reynolds S, Berk SL (1996) Effect of interferon alpha on HLA-DR expression by human buccal epithelial cells. Arch Immu­nol Ther Exp (Warsz) 44: 83-88.
• Smith JK, Siddiqui AA, Krishnaswamy GA, Dykes R, Berk SL, Magee M, Joyner W, Cummins J (1999) Oral use of interferon-alpha stimulates ISG-15 transcription and pro­duction by human buccal epithelial cells. J Interferon Cytokine Res 19: 923-928.
• Stanton GJ, Lloyd RE, Sarzotti M, Blalock JE (1989) Pro­tection of mice from Semliki Forest virus infection by lymphocytes treated with low levels of interferon. Mol Biother 1: 305-310.
• Taira O, Watanugi I, Hagiwara Y, Takahashi M, Arai S, Sato H, Maehara N (2005) Cloning and expression of canine interferon-alpha genes in Escherichia coli. J Vet Med Sci 67: 1059-1062.
• Takashinoue T, Keiji I,Taro S, Slaton JW, Kedar D, Dinney CP (2001) Inhibition of angiogenesis by interferon-alpha in human transitional cell carcinoma growing orthotopically in nude mice and study of combination therapy with cytoreductive chemotherapy. NHJUA 63: 223-227.
• Takayama S, Iwaki K, Nishida Y, Tanaka M, Fujii M, Ohashi K, Ikeda M, Kurimoto M (1999) Effects of oral adminis­tration of interferon-alpha on antibody production in mice with induced tolerance. J Interferon Cytokine Res 19: 895-900
• Tompkins WA (1999) Immunomodulation and therapeutic effects of the oral use of interferon-alpha: mechanism of action. J Interferon Cytokine Res 19: 817-828.
• Toomey NL, Deyev VV, Wood C, Boise LH, Scott D, Liu LH, Cabral L, Podack ER, Barber GN, Harrington WJ Jr (2001) Induction of a TRAIL-mediated suicide program by interferon alpha in primary effusion lymphoma. On­cogene 20: 7029-7040.
• Toth T, Cummins J. and Moore C (1994) Effects of very-low-dose oral cytokine treatment on hematological values in feline leukemia positive cells. J. Interferon Res 14: 187.
• Tovey MG, Maury C (1999) Oromucosal interferon therapy: marked antiviral and antitumor activity. J Interferon Cytokine Res 19: 145-155.
• Treanor JJ, Betts RF, Erb SM, Roth FK, Dolin R (1987) Intranasally administered interferon as prophylaxis against experimentally induced influenza A virus infec­tion in humans. J Infect Dis 156 :379-383.
• Valentine AD, Meyers CA, Kling MA, Richelson E, Hauser P (1998) Mood and cognitive side effects of inter­feron-alpha therapy. Semin Oncol 25 (1 Suppl 1): 39-47.
• Zeidner NS, Mathiason-DuBard CK, Hoover EA (1995) Reversal of feline leukemia virus infection by adoptive transfer of activated T lymphocytes, interferon alpha, and zidovudine. Semin Vet Med Surg (Small Anim)10: 256-266.
• Xing Z, Wang J (2000) Consideration of Cytokines as Therapeutics Agents or Targets. Curr Pharm Des 6: 599-611.
• Yanai Y, Sanou O, Kayano T, Ariyasu H, Yamamoto K, Yamauchi H, Ikegami H, Kurimoto M (2001) Analysis of the antiviral activities of natural IFN-alpha preparations and their subtype compositions. J Interferon Cytokine Res 21: 835-841.
• Young AS, Maritim AC, Kariuki DP, Stagg DA, Wafula JM, Mutugi JJ, Cummins JM, Richards AB, Burns C (1990) Low-dose oral administration of human interferon alpha can control the development of Theileria paiva infection in cattle. Parasitology 101: 201-209.