Skip to main content

Advertisement

Log in

Endotoxemia in febrile patients with hematological malignancies. Relationship of type of bacteremia, clinical findings and serum cytokine pattern

  • Originalia
  • Published:
Infection Aims and scope Submit manuscript

Summary

The relation between gram-negative bacteremia, endotoxemia and cytokinemia in patients with hematological malignancies was studied. Serum endotoxin and cytokines (tumor necrosis factor-α, interleukin-1 receptor antagonist, interferon-γ, interleukin-6 and interleukin-10) were determined in 24 patients with hematological malignancies. Patients were included at start of fever (n=18) or during a temperature peak during continuous fever (n=6; time=0). Blood was drawn for cultures at time of inclusion. Additional samples were obtained and grouped in two time intervals (1–5 h and 6–12 h after inclusion). Endotoxin was detected in eight patients. Endotoxemia was more common among patients with bacteremia than among non-bacteremic patients (7/12 versus 1/12; p<0.05). All studied cytokines showed a tendency to higher mean values at time 0 in patients with endotoxemia than in patients without endotoxemia. Significantly higher mean endotoxin values were seen at time 1–5 h in patients with gram-negative bacteremia (n=6) than in patients without gram-negative bacteremia, and at time 0 in patients with chills (n=6) compared to those without chills.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rietschel, E. T., Kirikae, T., Schade, F. U., Mamat, U., Schmidt, G., Loppnow, H., Ulmer, A. J., Zähringer, U., Seydel, U., Di Padova, F., Schreier, M., Brade, H. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 8 (1994) 217–225.

    PubMed  Google Scholar 

  2. van Deventer, S. J. H., Buller, H. R., ten Cate, J. W., Sturk, A., Pauw, W. Endotoxaemia: an early predictor of septicaemia in febrile patients. Lancet ii (1988) 605–609.

    Google Scholar 

  3. Danner, R. L., Elin, R. J., Hosseini, J. M., Wesley, R. A., Reilly, J. M., Parillo, J. E. Endotoxemia in human septic shock. Chest 99 (1991) 169–175.

    PubMed  Google Scholar 

  4. Dofferhoff, A. S., Vellenga, E., Limburg, P. C., van Zanten, A., Mulder, P. O., Weits, J. Tumour necrosis factor (cachectin) and other cytokines in septic shock: a review of the literature. Neth. J. Med. 39 (1991) 45–62.

    PubMed  Google Scholar 

  5. Dinarello, C. A. The biology of interleukin 1 and comparison to tumor necrosis factor. Immunol. Lett. 16 (1987) 227–232.

    PubMed  Google Scholar 

  6. Waage, A., Brandtzaeg, P., Halstensen, A., Kierulf, P., Espevik, T. The complex pattern of cytokines in serum from patients with meningococcal septic shock. J. Exp. Med. 169 (1989) 333–338.

    PubMed  Google Scholar 

  7. Harris, A., Rossberg, M. I., Hodes, H. L., Hyatt, A. C., Hodes, D. S. Endotoxinemia as a cause of fever in immunosuppressed patients. J. Clin. Pathol. 37 (1986) 467–470.

    Google Scholar 

  8. Behre, G., Schedel, I., Nentwig, B., Wörmann, B., Essink, M., Hiddemann, W. Endotoxin concentration in neutropenic patients with suspected gram-negative sepsis: correlation with clinical outcome and determination of anti-endotoxin core antibodies during therapy with polyclonal immunoglobulin M-enriched immunoglobulins. Antimicrob. Agents Chemother. 36 (1992) 2139–2146.

    PubMed  Google Scholar 

  9. McCartney, A. C., Robertson, M. R. I., Piotrowicz, B. I., Lucie, N. P. Endotoxaemia, fever and clinical status in immunosuppressed patients: a preliminary study. J. Infect. 15 (1987) 201–206.

    PubMed  Google Scholar 

  10. Kinsey, S. E., Machin, S. J. Endotoxinaemia in neutropenic patients. Lancet ii (1988) 345.

    Google Scholar 

  11. Shands, J. J. W., McKimmey, C. Plasma endotoxin: increased levels in neutropenic patients do not correlate with fever. J. Infect. Dis. 159 (1989) 777–780.

    PubMed  Google Scholar 

  12. Engervall, P., Granström, M., Andersson, B., Björkholm, M. Monitoring of endotoxin, interleukin-6 and C-reactive protein serum concentrations in neutropenic patients with fever. Eur. J. Haematol. 54 (1995) 226–234.

    PubMed  Google Scholar 

  13. Günther, G., Gårlund, B., Hast, R., Kimby, E., Nordin, M., Wretlind, B. Endotoxaemia and inflammatory mediators in febrile patients with haematological disease. J. Intern Med. 237 (1995) 27–33.

    PubMed  Google Scholar 

  14. Heney, D., Lewis, I. J., Evans, S. W., Banks, R., Bailey, C. C., Whicher, J. T. Interleukin-6 and its relationship to C-reactive protein and fever in children with febrile neutropenia. J. Infect. Dis. 165 (1992) 886–890.

    PubMed  Google Scholar 

  15. Riikonen, P., Saarinen, U. M., Teppo, A. M., Metsärinne, K., Fyhrquist, F., Jalanko, H. Cytokine and acute-phase reactant levels in serum of children with cancer admitted for fever and neutropenia. J. Infect. Dis. 166 (1992) 432–436.

    PubMed  Google Scholar 

  16. Waage, A., Remick, D., Stienshamm, S., Deforge, L., Lamvik, J. Interleukin 8 in serum in granulocytopenic patients with infections. Br. J. Haematol. 86 (1994) 36–40.

    PubMed  Google Scholar 

  17. Cebon, J., Layton, J. E., Maher, D., Morstyn, G. Endogenous haemopoietic growth factors in neutropenia and infection. Br. J. Haematol. 86 (1994) 265–274.

    PubMed  Google Scholar 

  18. Osterman, H., Rothenburger, M., Mesters, R. M., van de Loo, J., Kienast, J. Cytokine response to infection in patients with acute myelogenous leukemia following intensive chemotherapy. Br. J. Haematol. 88 (1994) 332–337.

    PubMed  Google Scholar 

  19. Engervall, P., Andersson, B., Björkholm, M. Clinical significance of serum cytokine patterns during start of fever in patients with neutropenia. Br. J. Haematol. 91 (1995) 838–845.

    PubMed  Google Scholar 

  20. Rintala, E., Pulkki, K., Mertsola, J., Nevalainen, T., Nikoskelainen, J. Endotoxin, interleukin-6 and phospholipase-A2 as markers of sepsis in patients with hematological malignancies. Scand. J. Infect. Dis. 27 (1995) 39–43.

    PubMed  Google Scholar 

  21. Antonelli, M., Raponi, G. M., Martino, P., Rosa, G., Conti, G., Jalouk, J., Gaspareto, A. High IL-6 serum levels are associated with septic shock and mortality in septic patients with severe leukopenia due to hematological malignancies. Scand. J. Infect. Dis. 27 (1995) 381–384.

    PubMed  Google Scholar 

  22. Hoffman, W. D., Natanson, C. Endotoxin in septic shock. Anesth. Analg. 77 (1993) 613–624.

    PubMed  Google Scholar 

  23. Ghosh, S., Latimer, R. D., Gray, B. M., Harwood, R. J., Oduro, A. Endotoxin-induced organ injury. Crit. Care Med. 21 (1993) S19-S24.

    PubMed  Google Scholar 

  24. Suffredini, A. F., Fromm, R. E., Parker, M. M., Brenner, M., Kovacs, J. A., Wesley, R. A., Parrillo, J. E. The cardiovascular response of normal humans to the administration of endotoxin. N. Engl. J. Med. 321 (1989) 280–287.

    PubMed  Google Scholar 

  25. Cannon, J. G., Tompkins, R. G., Gelfand, J. A., Michie, H. R., Stanford, G. G., van der Meer, J. W. M., Endres, S., Lonnemann, G., Corsetti, J., Chernow, B., Wilmore, D. W., Wolff, S. M., Burke, J. F., Dinarello, C. A. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J. Infect. Dis. 161 (1990) 79–84.

    PubMed  Google Scholar 

  26. van Deventer, S. J. H., Büller, H. R., ten Cate, J. W., Aarden, L. A., Hack, C. E., Sturk, A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, complement pathways. Blood 76 (1990) 2520–2526.

    PubMed  Google Scholar 

  27. Dofferhoff, A. S. M., Bom, V. J. J., de Vries-Hospers, H. G., van Ingen, J., vd Meer, J., Hazenberg, B. P. C., Mulder, P. O. M., Weits, J. Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans. Crit. Care Med. 20 (1992) 185–192.

    PubMed  Google Scholar 

  28. McCartney, A. C., Banks, J. G., Clements, G. B., Sleigh, J. D., Tehrani, M., Ledibgham, I. M. Endotoxaemia in septic shock: clinical and post mortem correlations. Intensive Care Med. 9 (1983) 117–122.

    PubMed  Google Scholar 

  29. Brandtzaeg, P., Kierulf, P., Saugstad, P. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J. Infect. Dis. 159 (1989) 195–204.

    PubMed  Google Scholar 

  30. Deitch, E. Bacterial translocation of the gut flora. J. Trauma. 30 (1990) 184–189.

    Google Scholar 

  31. Hurley, J. C. Antibiotic-induced release of endotoxin: a reappraisal. Clin. Infect. Dis. 15 (1992) 840–854.

    PubMed  Google Scholar 

  32. Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., Wilmore, D. W. Detection of circulating tumor necrosis factor after endotoxin administration. N. Engl. J. Med. 318 (1988) 1481–1486.

    PubMed  Google Scholar 

  33. Hesse, D. G., Tracey, K. J., Fong, Y., Manogue, K. R., Palladino Jr., M. A., Cerami, A., Shires, G. T., Lowry, S. F. Cytokine appearance in human endotoxemia and primate bacteremia. Surg. Gynecol. Obstet. 166 (1988) 147–153.

    PubMed  Google Scholar 

  34. Beutler, B., Milsark, I. W., Cerami, A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 229 (1985) 977–980.

    Google Scholar 

  35. Ohlsson, K., Björk, P., Bergenfeldt, M., Hageman, R., Thompson, R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348 (1990) 550–552.

    PubMed  Google Scholar 

  36. Doherty, G. M., Lange, J. R., Langstein, H. N., Alexander, H. R., Buresh, C. M., Norton, J. A. Evidence for IFN-γ as a mediator of the lethality of endotoxin and tumor necrosis factor-α. J. Immunol. 149 (1992) 1666–1670.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Engervall, P., Björkholm, M., Granström, M. et al. Endotoxemia in febrile patients with hematological malignancies. Relationship of type of bacteremia, clinical findings and serum cytokine pattern. Infection 25, 2–7 (1997). https://doi.org/10.1007/BF02113498

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02113498

Keywords

Navigation