Effects of RP 55778, a tumor necrosis factor alpha synthesis inhibitor, on antiviral activity of dideoxynucleosides.
Abstract
Tumor necrosis factor alpha (TNF-alpha) is overexpressed during human immunodeficiency virus (HIV) infection. RP 55778, a TNF-alpha synthesis inhibitor, decreases HIV replication in monocytes/macrophages. Therapeutic use of RP 55778 in vivo, like that of other biological response modifiers, would theoretically require association with dideoxynucleosides. We have evaluated here the combinatory effects of zidovudine (AZT) or dideoxyinosine (ddI) and RP 55778. This TNF-alpha inhibitor antagonizes the antiviral effects of both dideoxynucleosides, especially AZT. The more favorable anti-HIV activity of ddI in resting cells may explain these unequal degrees of antagonism.
Full Text
The Full Text of this article is available as a PDF (159K).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baba M, Pauwels R, Balzarini J, Herdewijn P, De Clercq E, Desmyter J. Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro. Antimicrob Agents Chemother. 1987 Oct;31(10):1613–1617.[PMC free article] [PubMed] [Google Scholar]
- Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. [PubMed] [Google Scholar]
- Boussin F, Dormont D, Merrouche Y, Fleury H, Dubeaux D, Bequet D, Goasguen J, Brunet P. Possible involvement of HIV in neuropsychiatric episode in patient seronegative for two (or more) years. Lancet. 1987 Sep 5;2(8558):571–572. [PubMed] [Google Scholar]
- Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55. [PubMed] [Google Scholar]
- Clayette P, Le Grand R, Noack O, Vaslin B, Le Naour R, Benveniste O, Théodoro F, Frétier P, Dormont D. Tumor necrosis factor-alpha in serum of macaques during SIVmac251 acute infection. J Med Primatol. 1995 Feb;24(2):94–100. [PubMed] [Google Scholar]
- Gao WY, Shirasaka T, Johns DG, Broder S, Mitsuya H. Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. J Clin Invest. 1993 May;91(5):2326–2333.[PMC free article] [PubMed] [Google Scholar]
- Lähdevirta J, Maury CP, Teppo AM, Repo H. Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Sep;85(3):289–291. [PubMed] [Google Scholar]
- Le Naour R, Raoul H, Mabondzo A, Henin Y, Bousseau A, Dormont D. Treatment of human monocyte-derived macrophages with a TNF alpha synthesis inhibitor prior to HIV1 infection: consequences on cytokine production and viral replication. Res Virol. 1994 May-Aug;145(3-4):199–207. [PubMed] [Google Scholar]
- Mabondzo A, Aussage P, Bartholeyns J, Le Naour R, Raoul H, Romet-Lemonne JL, Dormont D. Bispecific antibody targeting of human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 to human macrophages through the Fc IgG receptor I mediates neutralizing effects in HIV-1 infection. J Infect Dis. 1992 Jul;166(1):93–99. [PubMed] [Google Scholar]
- Perno CF, Yarchoan R, Cooney DA, Hartman NR, Gartner S, Popovic M, Hao Z, Gerrard TL, Wilson YA, Johns DG, et al. Inhibition of human immunodeficiency virus (HIV-1/HTLV-IIIBa-L) replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2',3'-dideoxynucleosides. J Exp Med. 1988 Sep 1;168(3):1111–1125.[PMC free article] [PubMed] [Google Scholar]
- Poli G, Kinter A, Justement JS, Kehrl JH, Bressler P, Stanley S, Fauci AS. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782–785.[PMC free article] [PubMed] [Google Scholar]
- Rey MA, Spire B, Dormont D, Barre-Sinoussi F, Montagnier L, Chermann JC. Characterization of the RNA dependent DNA polymerase of a new human T-lymphotropic retrovirus (lymphadenopathy associated virus). Biochem Biophys Res Commun. 1984 May 31;121(1):126–133. [PubMed] [Google Scholar]
- Vyakarnam A, McKeating J, Meager A, Beverley PC. Tumour necrosis factors (alpha, beta) induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication. AIDS. 1990 Jan;4(1):21–27. [PubMed] [Google Scholar]
- Weissman D, Poli G, Bousseau A, Fauci AS. A platelet-activating factor antagonist, RP 55778, inhibits cytokine-dependent induction of human immunodeficiency virus expression in chronically infected promonocytic cells. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2537–2541.[PMC free article] [PubMed] [Google Scholar]
- Wright SC, Jewett A, Mitsuyasu R, Bonavida B. Spontaneous cytotoxicity and tumor necrosis factor production by peripheral blood monocytes from AIDS patients. J Immunol. 1988 Jul 1;141(1):99–104. [PubMed] [Google Scholar]
Abstract
Tumor necrosis factor alpha (TNF-alpha) is overexpressed during human immunodeficiency virus (HIV) infection. RP 55778, a TNF-alpha synthesis inhibitor, decreases HIV replication in monocytes/macrophages. Therapeutic use of RP 55778 in vivo, like that of other biological response modifiers, would theoretically require association with dideoxynucleosides. We have evaluated here the combinatory effects of zidovudine (AZT) or dideoxyinosine (ddI) and RP 55778. This TNF-alpha inhibitor antagonizes the antiviral effects of both dideoxynucleosides, especially AZT. The more favorable anti-HIV activity of ddI in resting cells may explain these unequal degrees of antagonism.