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. 1995 Dec;39(12):2696–2701. doi: 10.1128/aac.39.12.2696

Nonionic block copolymers potentiate activities of drugs for treatment of infections with Toxoplasma gondii.

F G Araujo 1, T Slifer 1
PMCID: PMC163015  PMID: 8593005

Abstract

We studied the interaction between drugs and the nonionic block copolymers CRL 8131 and CRL 8142 in the treatment of toxoplasmosis in murine models of the disease. Treatment of acute toxoplasmosis with copolymers alone caused slight prolongation of time to death but not survival. In contrast, significant survival occurred when mice were treated with either copolymer combined with doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone, which did not prevent mortality when used alone. Treatment with CRL 8131 plus sulfadiazine or pyrimethamine resulted in 50 or 40% survival, respectively. Treatment with the same copolymer plus a dose of clindamycin that protected 40% of the mice when used alone resulted in 100% survival. Treatment of toxoplasmic encephalitis with CRL 8131 plus an ineffective dose of atovaquone reduced the inflammation and numbers of Toxoplasma gondii cysts in the brain. Studies to investigate the drug-enhancing activity of CRL 8131 revealed that mice immunized with toxoplasma lysate plus copolymer had lymphocyte proliferation responses to T. gondii antigens significantly higher than those in mice immunized with lysate alone. Challenge of immunized mice with a lethal inoculum of T. gondii resulted in significant survival. Administration of CRL 8131 alone appeared to cause a down-regulation in the production of gamma interferon and up-regulation in the production of interleukin-2. No differences were noted in the production of tumor necrosis factor alpha between mice treated with CRL 8131 and controls.

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Selected References

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  1. Araujo F. G. Depletion of L3T4+ (CD4+) T lymphocytes prevents development of resistance to Toxoplasma gondii in mice. Infect Immun. 1991 May;59(5):1614–1619. doi: 10.1128/iai.59.5.1614-1619.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Araujo F. G., Huskinson-Mark J., Gutteridge W. E., Remington J. S. In vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against the cyst form of Toxoplasma gondii. Antimicrob Agents Chemother. 1992 Feb;36(2):326–330. doi: 10.1128/aac.36.2.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Araujo F. G., Huskinson J., Remington J. S. Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother. 1991 Feb;35(2):293–299. doi: 10.1128/aac.35.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Araujo F. G., Slifer T., Remington J. S. Rifabutin is active in murine models of toxoplasmosis. Antimicrob Agents Chemother. 1994 Mar;38(3):570–575. doi: 10.1128/aac.38.3.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brinkmann V., Sharma S. D., Remington J. S. Different regulation of the L3T4-T cell subset by B cells in different mouse strains bearing the H-2k haplotype. J Immunol. 1986 Nov 1;137(9):2991–2997. [PubMed] [Google Scholar]
  6. Candolfi E., Hunter C. A., Remington J. S. Roles of gamma interferon and other cytokines in suppression of the spleen cell proliferative response to concanavalin A and toxoplasma antigen during acute toxoplasmosis. Infect Immun. 1995 Mar;63(3):751–756. doi: 10.1128/iai.63.3.751-756.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Howerton D. A., Hunter R. L., Ziegler H. K., Check I. J. Induction of macrophage Ia expression in vivo by a synthetic block copolymer, L81. J Immunol. 1990 Mar 1;144(5):1578–1584. [PubMed] [Google Scholar]
  8. Hunter C. A., Remington J. S. Immunopathogenesis of toxoplasmic encephalitis. J Infect Dis. 1994 Nov;170(5):1057–1067. doi: 10.1093/infdis/170.5.1057. [DOI] [PubMed] [Google Scholar]
  9. Hunter C. A., Subauste C. S., Remington J. S. The role of cytokines in toxoplasmosis. Biotherapy. 1994;7(3-4):237–247. doi: 10.1007/BF01878489. [DOI] [PubMed] [Google Scholar]
  10. Hunter R. L., Bennett B. The adjuvant activity of nonionic block polymer surfactants. II. Antibody formation and inflammation related to the structure of triblock and octablock copolymers. J Immunol. 1984 Dec;133(6):3167–3175. [PubMed] [Google Scholar]
  11. Israelski D. M., Remington J. S. Toxoplasmic encephalitis in patients with AIDS. Infect Dis Clin North Am. 1988 Jun;2(2):429–445. [PubMed] [Google Scholar]
  12. Johnson L. L. A protective role for endogenous tumor necrosis factor in Toxoplasma gondii infection. Infect Immun. 1992 May;60(5):1979–1983. doi: 10.1128/iai.60.5.1979-1983.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Krahenbuhl J. L., Fukutomi Y., Gu L. Treatment of acute experimental toxoplasmosis with investigational poloxamers. Antimicrob Agents Chemother. 1993 Nov;37(11):2265–2269. doi: 10.1128/aac.37.11.2265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Luft B. J., Remington J. S. Toxoplasmic encephalitis in AIDS. Clin Infect Dis. 1992 Aug;15(2):211–222. doi: 10.1093/clinids/15.2.211. [DOI] [PubMed] [Google Scholar]
  15. Lundén A., Lövgren K., Uggla A., Araujo F. G. Immune responses and resistance to Toxoplasma gondii in mice immunized with antigens of the parasite incorporated into immunostimulating complexes. Infect Immun. 1993 Jun;61(6):2639–2643. doi: 10.1128/iai.61.6.2639-2643.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCabe R. E., Luft B. J., Remington J. S. Effect of murine interferon gamma on murine toxoplasmosis. J Infect Dis. 1984 Dec;150(6):961–962. doi: 10.1093/infdis/150.6.961. [DOI] [PubMed] [Google Scholar]
  17. Sander B., Höidén I., Andersson U., Möller E., Abrams J. S. Similar frequencies and kinetics of cytokine producing cells in murine peripheral blood and spleen. Cytokine detection by immunoassay and intracellular immunostaining. J Immunol Methods. 1993 Dec 3;166(2):201–214. doi: 10.1016/0022-1759(93)90361-a. [DOI] [PubMed] [Google Scholar]
  18. Sharma S. D., Hofflin J. M., Remington J. S. In vivo recombinant interleukin 2 administration enhances survival against a lethal challenge with Toxoplasma gondii. J Immunol. 1985 Dec;135(6):4160–4163. [PubMed] [Google Scholar]
  19. Snippe H., De Reuver M. J., Strickland F., Willers J. M., Hunter R. L. Adjuvant effect of nonionic block polymer surfactants in humoral and cellular immunity. Int Arch Allergy Appl Immunol. 1981;65(4):390–398. doi: 10.1159/000232780. [DOI] [PubMed] [Google Scholar]
  20. Suzuki Y., Conley F. K., Remington J. S. Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon. Infect Immun. 1990 Sep;58(9):3050–3055. doi: 10.1128/iai.58.9.3050-3055.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Suzuki Y., Orellana M. A., Schreiber R. D., Remington J. S. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988 Apr 22;240(4851):516–518. doi: 10.1126/science.3128869. [DOI] [PubMed] [Google Scholar]
  22. Wong S. Y., Remington J. S. Biology of Toxoplasma gondii. AIDS. 1993 Mar;7(3):299–316. doi: 10.1097/00002030-199303000-00001. [DOI] [PubMed] [Google Scholar]

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