Abstract
Prostaglandin A2 (PGA2) inhibited the replication of herpes simplex virus type 1 in rabbit and human cornea stromal cells at concentrations of 1 to 5 microM while causing significant toxicity at 55 to 150 microM. Despite favorable therapeutic indices in cultured cells, PGA2 was not effective as a therapeutic agent in the treatment of herpetic keratitis in a rabbit model. The sequelae of disease appeared more severe in animals receiving PGA2 than in untreated or placebo-treated controls. The recovery of virus from tissues of latently infected rabbits was not affected by therapy. PGA2 therapy alone induced breakdown of the blood-aqueous barrier, indicating that pharmacologically active concentrations of drug were achieved in the eye. Thus, PGA2 had antiviral activity, but its proinflammatory effects appeared to be more detrimental than beneficial in the treatment of herpetic keratitis.
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Selected References
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- Amici C., Giorgi C., Rossi A., Santoro M. G. Selective inhibition of virus protein synthesis by prostaglandin A1: a translational block associated with HSP70 synthesis. J Virol. 1994 Nov;68(11):6890–6899. doi: 10.1128/jvi.68.11.6890-6899.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ankel H., Mittnacht S., Jacobsen H. Antiviral activity of prostaglandin A on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon. J Gen Virol. 1985 Nov;66(Pt 11):2355–2364. doi: 10.1099/0022-1317-66-11-2355. [DOI] [PubMed] [Google Scholar]
- Ankel H., Turriziani O., Antonelli G. Prostaglandin A inhibits replication of human immunodeficiency virus during acute infection. J Gen Virol. 1991 Nov;72(Pt 11):2797–2800. doi: 10.1099/0022-1317-72-11-2797. [DOI] [PubMed] [Google Scholar]
- Bito L. Z., Baroody R. A., Miranda O. C. Eicosanoids as a new class of ocular hypotensive agents. 1. The apparent therapeutic advantages of derived prostaglandins of the A and B type as compared with primary prostaglandins of the E, F and D type. Exp Eye Res. 1987 Jun;44(6):825–837. doi: 10.1016/s0014-4835(87)80045-3. [DOI] [PubMed] [Google Scholar]
- Camras C. B., Bito L. Z., Eakins K. E. Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits. Invest Ophthalmol Vis Sci. 1977 Dec;16(12):1125–1134. [PubMed] [Google Scholar]
- Cousins S. W., Trattler W. B., Streilein J. W. Immune privilege and suppression of immunogenic inflammation in the anterior chamber of the eye. Curr Eye Res. 1991 Apr;10(4):287–297. doi: 10.3109/02713689108996334. [DOI] [PubMed] [Google Scholar]
- Goetzl E. J., Yang J., Xia M., Zeng L., So S. W., An S. Diverse mechanisms of specificity of human receptors for eicosanoids. Ann N Y Acad Sci. 1994 Nov 15;744:146–154. doi: 10.1111/j.1749-6632.1994.tb52731.x. [DOI] [PubMed] [Google Scholar]
- Hughes-Fulford M., McGrath M. S., Hanks D., Erickson S., Pulliam L. Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication. Antimicrob Agents Chemother. 1992 Oct;36(10):2253–2258. doi: 10.1128/aac.36.10.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
- Narumiya S. Prostanoid receptors. Structure, function, and distribution. Ann N Y Acad Sci. 1994 Nov 15;744:126–138. doi: 10.1111/j.1749-6632.1994.tb52729.x. [DOI] [PubMed] [Google Scholar]
- Needleman P., Turk J., Jakschik B. A., Morrison A. R., Lefkowith J. B. Arachidonic acid metabolism. Annu Rev Biochem. 1986;55:69–102. doi: 10.1146/annurev.bi.55.070186.000441. [DOI] [PubMed] [Google Scholar]
- O'Brien W. J., Guy J., Taylor J. L. Pathogenesis of corneal oedema associated with herpetic eye disease. Br J Ophthalmol. 1990 Dec;74(12):723–730. doi: 10.1136/bjo.74.12.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Brien W. J., Taylor J. L. The isolation of herpes simplex virus from rabbit corneas during latency. Invest Ophthalmol Vis Sci. 1989 Mar;30(3):357–364. [PubMed] [Google Scholar]
- Parker J., Ahrens P. B., Ankel H. Antiviral effect of cyclopentenone prostaglandins on vesicular stomatitis virus replication. Antiviral Res. 1995 Jan;26(1):83–96. doi: 10.1016/0166-3542(94)00067-i. [DOI] [PubMed] [Google Scholar]
- Santoro M. G., Benedetto A., Carruba G., Garaci E., Jaffe B. M. Prostaglandin A compounds as antiviral agents. Science. 1980 Aug 29;209(4460):1032–1034. doi: 10.1126/science.6157190. [DOI] [PubMed] [Google Scholar]
- Santoro M. G., Favalli C., Mastino A., Jaffe B. M., Esteban M., Garaci E. Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus. Arch Virol. 1988;99(1-2):89–100. doi: 10.1007/BF01311026. [DOI] [PubMed] [Google Scholar]
- Santoro M. G. Heat shock proteins and virus replication: hsp70s as mediators of the antiviral effects of prostaglandins. Experientia. 1994 Nov 30;50(11-12):1039–1047. doi: 10.1007/BF01923459. [DOI] [PubMed] [Google Scholar]
- Stjernschantz J., Bito L. Z. The ocular effects of eicosanoids and other autacoids: historic background and the need for a broader perspective. Prog Clin Biol Res. 1989;312:1–13. [PubMed] [Google Scholar]
- Taylor J. L., O'Brien W. J., Goldman A. I. The determination of effective antiviral doses using a computer program for sigmoid dose-response curves. J Virol Methods. 1984 May;8(3):225–232. doi: 10.1016/0166-0934(84)90017-x. [DOI] [PubMed] [Google Scholar]
- Wander A. H., Centifanto Y. M., Kaufman H. E. Strain specificity of clinical isolates of herpes simplex virus. Arch Ophthalmol. 1980 Aug;98(8):1458–1461. doi: 10.1001/archopht.1980.01020040310020. [DOI] [PubMed] [Google Scholar]
- Wang R. F., Camras C. B., Lee P. Y., Podos S. M., Bito L. Z. Effects of prostaglandins F2 alpha, A2, and their esters in glaucomatous monkey eyes. Invest Ophthalmol Vis Sci. 1990 Nov;31(11):2466–2470. [PubMed] [Google Scholar]
- Yamamoto N., Fukushima M., Tsurumi T., Maeno K., Nishiyama Y. Mechanism of inhibition of herpes simplex virus replication by delta 7-prostaglandin A1 and delta 12-prostaglandin J2. Biochem Biophys Res Commun. 1987 Aug 14;146(3):1425–1431. doi: 10.1016/0006-291x(87)90809-6. [DOI] [PubMed] [Google Scholar]
- Yamamoto N., Rahman M. M., Fukushima M., Maeno K., Nishiyama Y. Involvement of prostaglandin-induced proteins in the inhibition of herpes simplex virus replication. Biochem Biophys Res Commun. 1989 Jan 16;158(1):189–194. doi: 10.1016/s0006-291x(89)80196-2. [DOI] [PubMed] [Google Scholar]
