Abstract
Assay of cytokines and C reactive protein (CRP) in different periods of febrile neutropenia may be helpful for early defining the risk in severe infections. We determined serum interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and CRP in 22 previously untreated patients with various malignancies. Samples were obtained in four different clinical periods of febrile neutropenia; prior to chemotherapy, afebrile neutropenic period after chemotherapy, febrile neutropenic period, and recovery period. When compared to sex-and age-matched group of healthy subjects, IL-6, IL-8, sIL-2R, and CRP levels were found to be elevated in all periods. The highest levels were encountered in the febrile neutropenic period. For predictivity purposes, the afebrile neutropenic period was the most important period. Serum sIL-2R, IL-6, IL-8 and CRP levels were elevated in this period. IL-8 levels showed the most stable elevation through different stages of febrile neutropenia. Serum IL-8 levels were found to have the most reliable and stable elevation in different clinical stages of febrile neutropenia. Nevertheless, IL-8 is not able to discriminate among risk groups and cannot be used as a predictive factor.
Similar content being viewed by others
References
Talcott JA, Whalen A, Clark J, Rieker PP, Finberg R. Home antibiotic therapy for low-risk cancer patients with fever and neutropenia: a pilot study of 30 patients based on a validated prediction rule. J Clin Oncol. 1994;12:107–14.
Malik IA, Khan WA, Karim M, Aziz Z, Khan MA. Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial. Am J Med. 1995;98:224–31. doi:10.1016/S0002-9343(99)80367-2.
Mustafa MM, Aquino VM, Pappo A, Tkaczewski I, Buchanan GR. A pilot study of outpatient management of febrile neutropenic children with cancer at low risk of bacteremia. J Pediatr. 1996;128:847–9. doi:10.1016/S0022-3476(96)70339-6.
Mullen CA, Petropoulos D, Roberts WM, Rytting M, Zipf T, Chan KW, et al. Outpatient treatment of fever and neutropenia for low risk pediatric cancer patients. Cancer. 1999;86:126–34. doi :10.1002/(SICI)1097-0142(19990701)86:1<126::AID-CNCR18>3.0.CO;2-1.
Talcott JA. Out-patient management of febrile neutropenia. Int J Antimicrob Agents. 2000;16:169–71. doi:10.1016/S0924-8579(00)00235-1.
Talcott JA, Finberg R, Mayer RJ, Goldman L. The medical course of cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation. Arch Intern Med. 1988;148:2561–8. doi:10.1001/archinte.148.12.2561.
Talcott JA, Siegel RD, Finberg R, Goldman L. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol. 1992;10:316–22.
Klaassen RJ, Goodman TR, Pham B, Doyle JJ. ‘Low-risk’ prediction rule for pediatric oncology patients presenting with fever and neutropenia. J Clin Oncol. 2000;18:1012–9.
Bodey GP, Buckley M, Sathe YS, Paesmans M. Risk factors assessment in febrile neutropenia. Int J Antimicrob Agents. 2000;16:107–11. doi:10.1016/S0924-8579(00)00241-7.
Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, et al. The Multinational Association for supportive care in cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18:3038–51.
Kern WV. Risk assessment and treatment of low-risk patients with febrile neutropenia. Clin Infect Dis. 2006;42:533–40. doi:10.1086/499352.
Lehrnbecher T, Venzon D, de Haas M, Chanock S, Kuhl J. Assessment of measuring circulating levels of interleukin-6, interleukin-8, C-reactive protein, soluble Fc gamma receptor type III and mannose-binding protein in febrile children with cancer and neutropenia. Clin Infect Dis. 1999;29:414–9. doi:10.1086/520224.
Waage A, Remick D, Steinshamn S, Deforge L, Lamvik J. Interleukin 8 in serum in granulocytopenic patients with infections. Br J Haematol. 1994;86:36–40. doi:10.1111/j.1365-2141.1994.tb03249.x.
Herrmann JL, Blanchard H, Brunengo P, Lagrange PH. TNF alpha, IL-1 beta and IL-6 plasma levels in neutropenic patients after onset of fever and correlation with the C-reactive protein (CRP) kinetic values. Infection. 1994;22:309–15. doi:10.1007/BF01715533.
Engervall P, Granstrom M, Andersson B, Bjorkholm M. Monitoring of endotoxin, interleukin-6 and C-reactive protein serum concentrations in neutropenic patients with fever. Eur J Haematol. 1995;54:226–34.
Engervall P, Andersson B, Björkholm M. Clinical significance of serum cytokine patterns during start of fever in patients with neutropenia. Br J Haematol. 1995;91:838–45. doi:10.1111/j.1365-2141.1995.tb05398.x.
Pechumer H, Wilhelm M, Ziegler-Heitbrock HW. Interleukin-6 levels in febrile children during maximal aplasia after bone marrow transplantation are similar to those in children with normal hematopoiesis. Ann Hematol. 1995;70:309–12. doi:10.1007/BF01696617.
Ostermann H, Rothenburger M, Mesters RM, van de LJ, Kienast J. Cytokine response to infection in patients with acute myelogenous leukaemia following intensive chemotherapy. Br J Haematol. 1994;88:332–7. doi:10.1111/j.1365-2141.1994.tb05027.x.
de Bont ES, Vellenga E, Swaanenburg JC, Fidler V, Visser-van Brummen PJ, Kamps WA. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia. Br J Haematol. 1999;107:375–80. doi:10.1046/j.1365-2141.1999.01707.x.
Stryjewski GR, Nylen ES, Bell MJ, Snider RH, Becker KL, Wu A, et al. Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children. Pediatr Crit Care Med. 2005;6:129–35. doi:10.1097/01.PCC.0000149317.15274.48.
Engel A, Mack E, Kern P, Kern WV. An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients. Infection. 1998;26:213–21.
Fleischhack G, Kambeck I, Cipic D, Hasan C, Bode U. Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II. Br J Haematol. 2000;111:1093–102. doi:10.1046/j.1365-2141.2000.02458.x.
Kern WV, Heiss M, Steinbach G. Prediction of Gram-negative bacteremia in patients with cancer and febrile neutropenia by means of ınterleukin-8 levels in serum: targeting empirical monotherapy versus combination therapy. Clin Infect Dis. 2001;32:832–5. doi:10.1086/319207.
Abrahamsson J, Pahlman M, Mellander L. Interleukin 6, but not tumour necrosis factor-alpha, is a good predictor of severe infection in febrile neutropenic and non-neutropenic children with malignancy. Acta Paediatr. 1997;86:1059–64. doi:10.1111/j.1651-2227.1997.tb14807.x.
Heney D, Lewis IJ, Evans SW, Banks R, Bailey CC, Whicher JT. Interleukin-6 and its relationship to C-reactive protein and fever in children with febrile neutropenia. J Infect Dis. 1992;165:886–90.
Engel A, Kern WV, Mürdter G, Kern P. Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumour necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia. Infection. 1994;2:160–3. doi:10.1007/BF01716695.
von Lilienfeld-Toal M, Dietrich MP, Glasmacher A, Lehmann L, Breig P, Hahn C, et al. Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein. Eur J Clin Microbiol Infect Dis. 2004;23:539–44. doi:10.1007/s10096-004-1156-y.
Mackie PH, Crockson RA, Stuart J. C-reactive protein for rapid diagnosis of infection in leukaemia. J Clin Pathol. 1979;32:1253–6. doi:10.1136/jcp. 32.12.1253.
Katz JA, Mustafa MM, Bash RO, Cash JV, Buchanan GR. Value of C-reactive protein determination in the initial diagnostic evaluation of the febrile, neutropenic child with cancer. Pediatr Infect Dis. 1992;11:708–12.
Manian FA. A prospective study of daily measurement of C-reactive protein in serum of adults with neutropenia. Clin Infect Dis. 1995;21:114–21.
Lindemann A, Tamm I, Tanodi K, Mertelsmann R. Interleukin-8 serum levels for early detection of infections episodes in neutropenic patients. J Infect Dis. 1995;172:610–3.
Schonbohn H, Schuler M, Kolbe K, Peschel C, Huber C, Bemb W, et al. Plasma levels of IL-1, TNF alpha, IL-6, IL-8, G-CSF, and IL1-R A during febrile neutropenia: results of a prospective study in patients undergoing chemotherapy for acute myelogenous leukemia. Ann Hematol. 1995;71:161–8. doi:10.1007/BF01910312.
Engel A, Steinbach G, Kern P, Kern WV. Diagnostic value of procalcitonin serum levels in neutropenic patients with fever: comparison with interleukin-8. Scand J Infect Dis. 1999;31:185–9. doi:10.1080/003655499750006254.
Engel A, Knoll SA, Kern P, Kern WV. Interleukin-8 serum levels at fever onset in patients with neutropenia predict early medical complications. Infection. 2005;33:380–2. doi:10.1007/s15010-005-5068-2.
Persson L, Engervall P, Magnuson A, Vikerfors T, Söderquist B, Hansson LO, et al. Use of inflammatory markers for early detection of bacteraemia in patients with febrile neutropenia. Scand J Infect Dis. 2004;36:365–71. doi:10.1080/00365540410020217.
Erten N, Genc S, Besisik SK, Saka B, Karan MA, Tascioglu C. The predictive and diagnostic values of procalcitonin and C-reactive protein for clinical outcome in febrile neutropenic patients. J Chin Med Assoc. 2004;67:217–21.
Persson L, Söderquist B, Engervall P, Vikerfors T, Hansson LO, Tidefelt U. Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia. Eur J Haematol. 2005;74:297–303. doi:10.1111/j.1600-0609.2004.00387.x.
Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34:730–51. doi:10.1086/339215.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Buyukberber, N., Buyukberber, S., Sevinc, A. et al. Cytokine concentrations are not predictive of bacteremia in febrile neutropenic patients. Med Oncol 26, 55–61 (2009). https://doi.org/10.1007/s12032-008-9081-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-008-9081-z