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Bacterial translocation from the gastrointestinal tracts of mice receiving immunosuppressive chemotherapeutic agents

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Abstract

Specific pathogen-free (SPF) mice were treated with certain classes of immunosuppressive chemotherapeutic agents to determine if they would promote bacterial translocation from the gastrointestinal tract to the mesenteric lymph node, spleen, or liver. The antimetabolites methotrexate, 5-fluorouracil, and cytosine arabinoside were injected once intraperitoneally into SPF mice, and the mice were tested for bacterial translocation from the gastrointestinal tract. When total organs from the treated mice were compared with the total organs from the control mice, the alkylating agent cyclophosphamide promoted bacterial translocation when injected once intraperitoneally at doses of 100–400 mg/kg. Increasing the number of injections of cyclophosphamide did not increase the incidence of bacterial translocation. The steroid prednisone also promoted bacterial translocation after one intraperitoneal injection of 10–150 mg/kg. Prednisone and cyclophosphamide at various doses appeared to be more effective in promoting bacterial translocation from the gastrointestinal tract than the antimetabolites. The aerobic and facultatively anaerobic bacteria translocating to the various organs were identified asLactobacillus acidophilus, Escherichia coli, Klebsiella pneumoniae, Streptococcus faecalis, Staphylococcus aureus, andProteus mirabilis. Groups of SPF mice also were injected once intraperitoneally with the minimal dose of each chemotherapeutic drug that induced bacterial translocation, and then tested for immune responsiveness toE. coli vaccination. Each of the chemotherapeutic agents at the minimal doses promoting bacterial translocation also suppressed the serum antibody responses to antigens of indigenousE. coli. However, other toxic manifestations of these chemotherapeutic agents also may be involved in promoting bacterial translocation. The promotion of bacterial translocation from the gastrointestinal tract by these chemotherapeutic agents has important implications for the pathogenesis of infectious disease in patients receiving these drugs.

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Literature Cited

  1. Altmann, G. G. 1974. Changes in the mucosa of the small intestine following methotrexate administration or abdominal X-irradiation. American Journal of Anatomy140:263–279.

    Google Scholar 

  2. Amaku, E. O., May, A. G., Hall, T. C., Linke, C. A. 1971. Prolongation of mouse skin allograft survival by treatment with cytosine arabinoside in combination with F-1 hydrid lymphocytes. Transplantation12:249–252.

    Google Scholar 

  3. Annana, A., Eloy, R., Bouchet, P., Clendinnen, G., Grenier, J. F. 1979. Effects of oral and parenteral corticosteroids on intestinal villous morphology and brush border enzymes in rats. Laboratory investigations41:83–88.

    Google Scholar 

  4. Baskerville, A., Batter-Hatton, D. 1977. Intestinal lesions induced experimentally by methotrexate. British Journal of Experimental Pathology58:663–669.

    Google Scholar 

  5. Berg, R. D. 1980. Inhibition ofEscherichia coli translocation from the gastrointestinal tract by normal cecal flora in gnotobiotic or antibiotic-decontaminated mice. Infection and Immunity29:1073–1081.

    Google Scholar 

  6. Berg, R. D. 1981. Promotion of the translocation of enteric bacteria from the gastrointestinal tract by oral treatment with penicillin, clindamycin or metronidazole. Infection and Immunity33:854–861.

    Google Scholar 

  7. Berg, R. D., Garlington, A. W. 1979. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infection and Immunity23:403–411.

    Google Scholar 

  8. Berg, R. D., Garlington, A. W. 1980. Translocation ofEscherichia coli from the gastrointestinal tract to the mesenteric lymph nodes in gnotobiotic mice receivingEscherichia coli vaccines before colonization. Infection and Immunity30:894–898.

    Google Scholar 

  9. Berg, R. D., Owens, W. E. 1979. Inhibition of translocation of viableEscherichia coli from the gastrointestinal tract of mice by bacterial antagonism. Infection and Immunity25:820–827.

    Google Scholar 

  10. Bodey, G. P., McCredie, K. B., Rodriguez, V., Freireich, F. J. 1975. Management of infectious complications of cancer chemotherapy, pp. 357–368. In: Fundamental concepts and recent advances. Chicago: Yearbook Medical Publishers, Inc.

    Google Scholar 

  11. Buchanan, R. E., Gibbons, N. E. 1974. Bergey's manual of determinative bacteriology, 8th ed. Baltimore: The Williams and Wilkins Co.

    Google Scholar 

  12. Dubois, M., Gilles, K. A., Hamilton, J. K., Rebers, T. A., Smith, F. S. 1956. Colorimetric method of determination of sugars and related substances. Annals of Chemistry28:350–356.

    Google Scholar 

  13. Eloy, R., Vuitton, D., Vaultier, J.-P., Klein, M., Grenier, J. F. 1976. Cortisone sensitive T-cells in Peyer's patches. Experentia32:647–649.

    Google Scholar 

  14. Harrison, S. D., Denine, E. P., Peckham, J. C. 1978. Qualitative and quantitative toxicity of single and sequential sublethal doses of 5-fluorouracil in BDF1 mice. Cancer Treatment Reports62:533–545.

    Google Scholar 

  15. Hughes, W. T. 1977. Infections in the compromised host. Advances in Internal Medicine22:73–96.

    Google Scholar 

  16. Hurd, E. R. 1977. Drugs affecting the immune response, pp. 1067–1099. In: Holborow, E. J., Reeves, H. G. (eds.), Immunology in medicine.

  17. Hyams, J. S., Donaldson, M. H. Metcalf, J. A., Root, R. K. 1978. Inhibition of human granulocyte function by methotrexate. Cancer Research38:650–655.

    Google Scholar 

  18. Jeyner, B. J., Altmann, G. G. 1978. Light and scanning electron microscopic observations of the effects of sublethal doses of methotrexate on the rat small intestines. Anatomical Record191:1–8.

    Google Scholar 

  19. Lane, M. 1959. Preliminary report of animal studies with cytoxan (cyclophosphamide). Cancer Chemotherapy Reports3:1–5.

    Google Scholar 

  20. Leach, W. B., Laster, Jr., W. R., Mayo, J. G., Griswold, Jr., D. P., Schabel, Jr., F. M. 1969. Toxicity studies in mice treated with 1-B-D-arabinofucanosylcytosine (ar-C). Cancer Research29:529–535.

    Google Scholar 

  21. Margolis, S., Phillips, F. S., Steinberg, S. S. 1971. The cytotoxicity of methotrexate in mouse small intestine in relation to inhibition of folic acid reductase and of DNA synthesis. Cancer Research31:2037–2046.

    Google Scholar 

  22. Merritt, K., Johnson, A. G. 1963. Studies on the adjuvant action of bacterial endotoxins on antibody formation. V. The influence of endotoxin and 5-fluoro-2-deoxyuridine on the primary antibody response of the BALB mouse to a purified protein antigen. Journal of Immunology91:266–272.

    Google Scholar 

  23. Muggia, A. L., Wayman, E., Miller, S. S., Spiro, H. M. 1963. Response of the gastrointestinal tract of the mouse to 5-fluorouracil. American Journal of Pathology42:407–414.

    Google Scholar 

  24. Owens, W. E., Berg, R. D. 1980. Inhibition by thymic grafts of bacterial translocation from the gastrointestinal tract in athymic (nu/nu) mice. Infection and Immunity27:461–467.

    Google Scholar 

  25. Owens, W. E., Berg, R. D. 1982. Bacterial translocation from the gastrointestinal tracts of thymectomized mice. Current Microbiology7:169–174.

    Google Scholar 

  26. Prierson, C. L., Johnson, A. G., Feller, I. 1976. Effect of cyclophosphamide on the immune response toPseudomonas aeruginosa in mice. Infection and Immunity14:168–177.

    Google Scholar 

  27. Salaman, J. R., Miller, J. J. 1979. Nonspecific chemical immunosuppression. Transplantation Proceedings11:845–850.

    Google Scholar 

  28. Schaedler, R. W., Dubos, R., Costello, R. 1965. The development of the bacterial flora in the gastrointestinal tract of mice. Journal of Experimental Medicine122:59–66.

    Google Scholar 

  29. Schreiber, A. D. 1977. Clinical immunology of the corticosteroids. Progress in Clinical Immunology4:103–114.

    Google Scholar 

  30. Sharbaugh, R. J., Grogan, J. B. 1969. Suppression of reticuloendothelial function in the rat with cyclophosphamide. Journal of Bacteriology100:117–122.

    Google Scholar 

  31. Siber, G. R., Mayer, R. J., Levin, M. J. 1980. Increased gastrointestinal absorption of large molecules in patients after 5-fluorouracil therapy from metastatic colon carcinoma. Cancer Research40:3430–3436.

    Google Scholar 

  32. Smith, P. B., Tomfohrd, K. M., Rhoden, D. L., Balows, A. 1972. API system: a multitube micromethod for identification ofEnterobacteriaceae. Applied Microbiology24:449–452.

    Google Scholar 

  33. Taminiau, J. A. J. M., Gall, D. G., Hamilton, J. R. 1980. Response of the rat small-intestine epithelium to methotrexate. Gut21:486–492.

    Google Scholar 

  34. Weir, D. M. 1967. Handbook of experimental immunology. Philadelphia: F. A. Davis Co.

    Google Scholar 

  35. Winkelstein, A. 1973. Differential effects of immunosuppressants on lymphocyte function. Journal of Clinical Investigation52:2293–2299.

    Google Scholar 

  36. Woodruff, R. 1978. The management of adult acute lymphoblastic leukaemia. Cancer Treatment Reviews5:95–113.

    Google Scholar 

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  1. Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport, 71130, Shreveport, Louisiana, USA

    Rodney D. Berg

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Berg, R.D. Bacterial translocation from the gastrointestinal tracts of mice receiving immunosuppressive chemotherapeutic agents. Current Microbiology 8, 285–292 (1983). https://doi.org/10.1007/BF01577729

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