Abstract
Dialysable Leucocyte Extract (DLE) is a low molecular weight dialysable material of disrupted peripheral human leucocytes with widespread effects on the immune system. We described thein vitro anti-HIV activity of DLE as well as its three chromatographic fractions (Fa, Fb and Fc). To determine the levels of inhibition on HIV replication by DLE we infected MT-4 cell cultures, using the Bru viral isolate at 0.05, 0.1, 0.5 and 1 m.o.i. Previously, MT-4 cells cultures were treated with DLE or fractions at non-toxic concentrations. Reverse transcriptase (RT) activity and p24 antigen were evaluated in culture supernatants at seven days postinfection. No effect was observed when MT-4 cells were incubated with DLE for 3 h. Whereas inhibition of HIV production was observed when MT-4 cells were pre-treated for a longer period of time. DLE inhibited p24 production and RT activity more than 50% at 0.1 m.o.i. More than 80% of inhibition was observed for all doses of DLE tested at 0.05 m.o.i. Higher viral doses (m.o.i. 0.5 and 1) were used to assess the antiviral activity of DLE fractions. Fraction Fb inhibits viral production more than 80%. Otherwise, fractions Fa and Fc did not show inhibitory effect for any viral dose used. These results indicate that DLE is able to modulate cell susceptibility to viral infectionin vitro.
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Abbreviations
- AIDS:
-
Acquired immunodeficiency syndrome
- DLE:
-
Dialysable leucocyte extract
- HIV:
-
Human immunodeficiency virus
- M.O.I.:
-
Multiplicity of infection
- RT:
-
Reverse transcriptase
References
Borrow P, Lewicki H, Hahn BH, Shaw GM & Oldstone, MBA. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary Human Immunodeficiency Virus type 1 infection. J Virol 1994; 68: 6103–10.
Saag MS, Hammer SM & Lange JMA. Pathogenicity and diversity of HIV and implications for clinical management: A review. J AIDS 1994; 7: S2-S11.
Stein DS, Timpone JG, Gradon JD, Kagan JM & Schnittman SM. Immune-based therapeutics: Scientific rationale and the promising approaches to the treatment of the HIV-infected individual. Clin Inf D 1993; 17: 749–71.
Salk PL & Salk J. Cell-mediated immunologic memory in prevention and treatment of HIV disease. Res Immunol 1994; 145: 629–35.
Lawrence HS: The transfer in humans of delayed skin sensitivity to streptococcal M substance and to tuberculin with disrupted leukocytes. J Clin Inv 1955; 34: 219–24.
Kirkpatrick CH & Greenberg LE. Treatment of chronic mucocutaneous candidiasis with Transfer Factor. In: Khan A, Kirkpatrick CH, Hill NO, eds. Immune regulators in Transfer Factor. New York: Academic Press, 1979: 547–59.
Gottlieb AA & Gottlieb MS. Clinical and biological effects of IMREG-1 and IMREG-2, two immunologically active components of leukocyte dialysates. In: Fujisawa T, Sasakawa S, eds. Recent advances in Transfer Factor and Dialyzable Leukocyte Extracts. Tokyo: Maruzen Co, 1990: 2–10.
Sargent IL, Salaman MR & Valdimarsson H. Effect of Transfer Factor (TF) and thymosin on the recovery of E-rosetting capacity in trypsinised lymphocytes. In: Khan A, Kirkpatrick CH, Hill NO, eds. Immune regulators in Transfer Factor. New York: Academic Press, 1979: 129–35.
Drofling P & Schroder I. Effect of Dialyzable Leukocyte Extract and its different fractions on the production of H2O2 and IL-1 by macrophages. In: Mayer V, Borvak J, eds. Leukocytes Dialysates and Transfer Factor. Bratislava: Slovak Academy, 1987: 141–45.
Fudenberg HH, Spitler LE & Levin AS. Treatment of immunodeficiency. Am J Path 1972; 69: 529–36.
Blume MR, Rosenbaum EH, Cohen RJ, Gershow J, Glassberg AB & Shepley E. Adyuvant Immunotherapy of high risk stage I melanoma with Transfer Factor. Cancer 1981; 47: 882–88.
Louie E, Borkowsky W, Klesius PH, Haynes TB, Gordon S, Bonk S & Lawrence HS. Treatment of cryptosporidiosis with oral bovine Transfer Factor. Clin Imm Im 1987; 44: 329–34.
Cabezas R, Estrada S, Padierna L, Fernandez-Ortega C & Lopez P. Inmuterapia con Factor de Transferencia en pacientes con herpes zoster. Biotecnologia Aplicada 1990; 7: 52–7.
Prochazkova J, Parizkova E, Horacek J, Pozler O, Chylkova V, Turkova M & Hanovcova I. Clinical and immunological improvement in infants with HCMV infection treated with DLE. In: Mayer V, Borvak J, eds. Leukocytes Dialysates and Transfer Factor. Bratislava: Slovak Academy, 1987: 403–11.
Roda E, Viza D, Pizza G, Mastroroberto L, Philips J, De Vinci C & Barbara L. Transfer Factor for the treatment of HBsAg-positive chronic active hepatitis. Proc Soc Exp Biol Med 1985; 178: 468–75.
Cabezas R, Estrada S, Padierna J, Ysla R, Diaz dela Rocha A, Sagaro B, Gonzalez E, Diaz Z, Cortina M, Fernandez-Ortega C & Lopez P. Effects of DLE in patients with herpes. In: Baolai H, Ruzhang W, Zhaofen Z, eds. Research and applications of Transfer Factor and DLE. Beijing: Xue Yuan Press, 1989: 294–307.
Carey JT, Michael MD, Lederman MM, Toossi Z, Edmonds K, Hodder S, Calabrese LH, Proffit MR, Johnson CE & Ellner JJ. Augmentation of skin test reactivity and lymphocyte blastogenesis in patients with AIDS treated with Transfer Factor. JAMA 1987; 257: 651–55.
Schmidtmayerova H, Chermann JC, Rey F, Barre-Sinoussi F & Mayer V. The effect of the lysed leukocyte ultrafiltrate on the HIV: in vitro study. In: Mayer V, Borvak J, eds. Leukocytes Dialysates and Transfer Factor. Bratislava: Slovak Academy, 1987: 366–76.
Lee MH, Sano K, Morales FE & Imagawa DT. Sensitive reverse transcriptase assay to detect and quantitate human immunodeficiency virus. J Clin Micr 1987; 25: 1717–21.
Yarchoan R, Mitsuya H & Broder S. Challenges in the therapy of HIV infection. Immunol Tod 1993; 14: 303–8.
Klesius P, McMeeking A, Borkowsky W, Bonk S, Holzman RS & Lawrence HS. Immunotherapy of cryptosporidium parvum with bovine Transfer Factor. In: Baolai H, Ruzhang W, Zhaofen Z, eds. Research and applications of Transfer Factor and DLE. Beijing: Xue Yuan Press, 1989: 227–38.
Butera ST, Roberts BD & Folks TM. Regulation of HIV-1 expression by cytokine networks in a CD4+ model of chronic infection. J Immunol 1993; 150: 625–34.
Poli G & Fauci AS. The effect of cytokines and pharmacologic agents on chronic HIV infection. AIDS Res Human Retro 1992; 8: 191–96.
Folks TM, Clouse KA, Justement JS, Rabson A, DuhE Kehrl JH & Fauci AS. Tumor necrosis factor alpha induces expression of HIV in a chronically infected T-cell clone. Proc Natl Acad Sci 1989; 86: 2365–69.
Harada S, Koyanagi Y & Yamamoto N. Infection of HTLV-III/LAV in HTLV-1-carrying cells MT-2 and MT-4 and application in a plaque assay. Science 1985; 229: 563–66.
Ito M, Baba M, Sato A, Hirabayashi K, Tanabe F, Shigeta S & DeClercq E. Tumor necrosis factor enhances replication of human immunodeficiency virus in vitro. Bioc Biop R 1989; 158: 307–12.
Kobayashi N, Hamamoto Y & Yamamoto N. Production of tumor necrosis factors by T cell lines infected with HTLV-1 may cause their high susceptibility to human immunodeficiency virus infection. Med Microbi 1990; 179: 115–22.
Borvak J & Schmidtmayerova H. Inhibition of HIV-1 reverse transcriptase activity by HPLC fractions of lysed leukocyte ultrafiltrate. In: Fujisawa T, Sasakawa S, eds. Recent Advances in Transfer Factor and Dialyzable Leukocyte Extracts. Tokyo: Maruzen Co, 1990: 87–93.
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Fernandez-Ortega, C., Dubed, M., Ruibal, O. et al. Inhibition of in vitro HIV infection by dialysable leucocyte extracts. Biotherapy 9, 33–40 (1996). https://doi.org/10.1007/BF02628654
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DOI: https://doi.org/10.1007/BF02628654