Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Feb;36(2):361–367. doi: 10.1128/aac.36.2.361

Prevention of indigenous infection of mice with Escherichia coli by nonspecific immunostimulation.

K Nomoto 1, T Yokokura 1, M Mitsuyama 1, Y Yoshikai 1, K Nomoto 1
PMCID: PMC188442  PMID: 1605602

Abstract

We have previously reported that the lethal toxicity of 5-fluorouracil (5-FU) in specific-pathogen-free mice is due to an intestinal infection with indigenous Escherichia coli induced by the drug (K. Nomoto, T. Yokokura, Y. Yoshikai, M. Mitsuyama, and K. Nomoto, Can J. Microbiol. 37:244-247, 1991). In the present study we demonstrate that nonspecific immunostimulation is effective in the protection of mice from the lethal indigenous infection induced by 5-FU. Intravenous or subcutaneous injection of a preparation of heat-killed Lactobacillus casei YIT 9018, a potent nonspecific immunostimulant, into BALB/c mice reduced the lethal toxicity of 5-FU at doses ranging from 338 to 800 mg/kg of body weight if YIT 9018 was injected 7 to 40 days before administration of 5-FU. Systemic infection with E. coli developed in all of the 5-FU-treated control mice 7 days or more after administration of 5-FU in large doses and was accompanied by overgrowth of the bacteria in the intestinal tract. Pretreatment of mice with YIT 9018 resulted in a decreased occurrence of systemic infection with E. coli to levels of 0 to 20% and no significant changes in the population levels of E. coli in the intestinal tract during the 14 days after administration of 5-FU. The levels of leukopenia in the spleen and peripheral blood were lower, and recovery of granulocyte-macrophage precursor cells in the spleen and femur began earlier in the treated animals than in the 5-FU-treated controls. Intravenous transfusion of syngeneic normal bone marrow cells or spleen cells into the mice at an early period after administration of 5-FU diminished markedly the occurrence of the lethal indigenous infection, suggestion that an earlier recovery from chemotherapy-induced myelosuppression is important in the mechanisms of protection of the host from the infection.

Full text

PDF
361

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Athlin L., Domellöf L. Effects of fluorouracil, doxorubicin and FAM combination on human peritoneal macrophages. Chemotherapy. 1987;33(4):287–290. doi: 10.1159/000238509. [DOI] [PubMed] [Google Scholar]
  2. Berg R. D., Garlington A. W. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun. 1979 Feb;23(2):403–411. doi: 10.1128/iai.23.2.403-411.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Connolly K. M., Diasio R. B., Armstrong R. D., Kaplan A. M. Decreased immunosuppression associated with antitumor activity of 5-deoxy-5-fluorouridine compared to 5-fluorouracil and 5-fluorouridine. Cancer Res. 1983 Jun;43(6):2529–2535. [PubMed] [Google Scholar]
  4. Foster R. S., Jr Altered toxicity of 5-fluorouracil following treatment with Corynebacterium parvum. Cancer Res. 1978 Mar;38(3):850–858. [PubMed] [Google Scholar]
  5. Foster R. S., Jr Effect of Corynebacterium parvum on the proliferative rate of granulocyte-macrophage progenitor cells and the toxicity of chemotherapy. Cancer Res. 1978 Sep;38(9):2666–2672. [PubMed] [Google Scholar]
  6. Fuller K. G., Berg R. D. Inhibition of bacterial translocation from the gastrointestinal tract by nonspecific immunostimulation. Prog Clin Biol Res. 1985;181:195–198. [PubMed] [Google Scholar]
  7. Glucksberg H., Cheever M. A., Farewell V. T., Fefer A., Sale G. E., Thomas E. D. High-dose combination chemotherapy for acute nonlymphoblastic leukemia in adults. Cancer. 1981 Sep 1;48(5):1073–1081. doi: 10.1002/1097-0142(19810901)48:5<1073::aid-cncr2820480504>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  8. Hashimoto S., Nomoto K., Matsuzaki T., Yokokura T., Mutai M. Oxygen radical production by peritoneal macrophages and Kupffer cells elicited with Lactobacillus casei. Infect Immun. 1984 Apr;44(1):61–67. doi: 10.1128/iai.44.1.61-67.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Keating M. J., Smith T. L., McCredie K. B., Bodey G. P., Hersh E. M., Gutterman J. U., Gehan E., Freireich E. J. A four-year experience with anthracycline, cytosine arabinoside, vincristine and prednisone combination chemotherapy in 325 adults with acute leukemia. Cancer. 1981 Jun 15;47(12):2779–2788. doi: 10.1002/1097-0142(19810615)47:12<2779::aid-cncr2820471204>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  10. Kreger B. E., Craven D. E., Carling P. C., McCabe W. R. Gram-negative bacteremia. III. Reassessment of etiology, epidemiology and ecology in 612 patients. Am J Med. 1980 Mar;68(3):332–343. doi: 10.1016/0002-9343(80)90101-1. [DOI] [PubMed] [Google Scholar]
  11. Maddaus M. A., Wells C. L., Platt J. L., Condie R. M., Simmons R. L. Effect of T cell modulation on the translocation of bacteria from the gut and mesenteric lymph node. Ann Surg. 1988 Apr;207(4):387–398. doi: 10.1097/00000658-198804000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Matsumoto M., Matsubara S., Matsuno T., Tamura M., Hattori K., Nomura H., Ono M., Yokota T. Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice. Infect Immun. 1987 Nov;55(11):2715–2720. doi: 10.1128/iai.55.11.2715-2720.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McIntyre K. W., Unowsky J., DeLorenzo W., Benjamin W. Enhancement of antibacterial resistance of neutropenic, bone marrow-suppressed mice by interleukin-1 alpha. Infect Immun. 1989 Jan;57(1):48–54. doi: 10.1128/iai.57.1.48-54.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miake S., Nomoto K., Yokokura T., Yoshikai Y., Mutai M., Nomoto K. Protective effect of Lactobacillus casei on Pseudomonas aeruginosa infection in mice. Infect Immun. 1985 May;48(2):480–485. doi: 10.1128/iai.48.2.480-485.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moore M. A., Warren D. J. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7134–7138. doi: 10.1073/pnas.84.20.7134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nanno M., Shimizu-Takeda T., Mike A., Ohwaki M., Togashi Y., Suzuki R., Kumagai K., Mutai M. Increased production of cytotoxic macrophage progenitors by Lactobacillus casei in mice. J Leukoc Biol. 1989 Aug;46(2):89–95. doi: 10.1002/jlb.46.2.89. [DOI] [PubMed] [Google Scholar]
  17. Nanno M., Shimizu T., Mike A., Ohwaki M., Mutai M. Role of macrophages in serum colony-stimulating factor induction by Lactobacillus casei in mice. Infect Immun. 1988 Feb;56(2):357–362. doi: 10.1128/iai.56.2.357-362.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nomoto K., Miake S., Hashimoto S., Yokokura T., Mutai M., Yoshikai Y., Nomoto K. Augmentation of host resistance to Listeria monocytogenes infection by Lactobacillus casei. J Clin Lab Immunol. 1985 Jun;17(2):91–97. [PubMed] [Google Scholar]
  19. Nomoto K., Yokokura T., Yoshikai Y., Mitsuyama M., Nomoto K. Induction of lethal infection with indigenous Escherichia coli in mice by fluorouracil. Can J Microbiol. 1991 Mar;37(3):244–247. doi: 10.1139/m91-037. [DOI] [PubMed] [Google Scholar]
  20. Ohta Y., Sueki K., Kitta K., Takemoto K., Ishitsuka H., Yagi Y. Comparative studies on the immunosuppressive effect among 5'-deoxy-5-fluorouridine, ftorafur, and 5-fluorouracil. Gan. 1980 Apr;71(2):190–196. [PubMed] [Google Scholar]
  21. Schwartz G. N., Neta R., Vigneulle R. M., Patchen M. L., MacVittie T. J. Recovery of hematopoietic colony-forming cells in irradiated mice pretreated with interleukin 1 (IL-1). Exp Hematol. 1988 Oct;16(9):752–757. [PubMed] [Google Scholar]
  22. Shimamura M., Kobayashi Y., Yuo A., Urabe A., Okabe T., Komatsu Y., Itoh S., Takaku F. Effect of human recombinant granulocyte colony-stimulating factor on hematopoietic injury in mice induced by 5-fluorouracil. Blood. 1987 Jan;69(1):353–355. [PubMed] [Google Scholar]
  23. Shimizu T., Nomoto K., Yokokura T., Mutai M. Role of colony-stimulating activity in antitumor activity of Lactobacillus casei in mice. J Leukoc Biol. 1987 Sep;42(3):204–212. doi: 10.1002/jlb.42.3.204. [DOI] [PubMed] [Google Scholar]
  24. Tancrède C. H., Andremont A. O. Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies. J Infect Dis. 1985 Jul;152(1):99–103. doi: 10.1093/infdis/152.1.99. [DOI] [PubMed] [Google Scholar]
  25. Tanikawa S., Nakao I., Tsuneoka K., Nara N. Effects of recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on acute radiation hematopoietic injury in mice. Exp Hematol. 1989 Sep;17(8):883–888. [PubMed] [Google Scholar]
  26. Wells C. L., Ferrieri P., Weisdorf D. J., Rhame F. S. The importance of surveillance stool cultures during periods of severe neutropenia. Infect Control. 1987 Aug;8(8):317–319. doi: 10.1017/s0195941700066406. [DOI] [PubMed] [Google Scholar]
  27. Wells C. L., Maddaus M. A., Reynolds C. M., Jechorek R. P., Simmons R. L. Role of anaerobic flora in the translocation of aerobic and facultatively anaerobic intestinal bacteria. Infect Immun. 1987 Nov;55(11):2689–2694. doi: 10.1128/iai.55.11.2689-2694.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wells C. L., Maddaus M. A., Simmons R. L. Proposed mechanisms for the translocation of intestinal bacteria. Rev Infect Dis. 1988 Sep-Oct;10(5):958–979. doi: 10.1093/clinids/10.5.958. [DOI] [PubMed] [Google Scholar]
  29. Wells C. L., Maddaus M. A., Simmons R. L. Role of the macrophage in the translocation of intestinal bacteria. Arch Surg. 1987 Jan;122(1):48–53. doi: 10.1001/archsurg.1987.01400130054008. [DOI] [PubMed] [Google Scholar]
  30. Wells C. L., Podzorski R. P., Peterson P. K., Ramsay N. K., Simmons R. L., Rhame F. S. Incidence of trimethoprim-sulfamethoxazole-resistant enterobacteriaceae among transplant recipients. J Infect Dis. 1984 Nov;150(5):699–706. doi: 10.1093/infdis/150.5.699. [DOI] [PubMed] [Google Scholar]
  31. Yokokura T., Nomoto K., Shimizu T., Nomoto K. Enhancement of hematopoietic response of mice by subcutaneous administration of Lactobacillus casei. Infect Immun. 1986 Apr;52(1):156–160. doi: 10.1128/iai.52.1.156-160.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES