The serum IL-12: IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation

R. A. Tuma, N. G. Almyroudis, S. J. Sohn, K. Panageas, R. D. Rice, D. Galinkin, M. Blain, M. Montefusco, E. G. Pamer, Stephen D Nimer, T. Kewalramani

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Fever during neutropenia and after neutrophil engraftment (post-engraftment fever) occurs commonly during autologous transplantation (ASCT), but infections are infrequently identified. Tests that reliably exclude infection may reduce the cost and toxicity of unnecessary diagnostic testing and empiric treatment. We assessed whether serum levels of inflammatory cytokines could distinguish infectious from non-infectious causes of fever in patients undergoing ASCT. Methods: Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL- 12(p70), TNF-α and IFN-γ were measured by sandwich ELISA at multiple pre-determined times and at the onset of the first fever during neutropenia and after neutrophil engraftment in patients with hematologic malignancies undergoing ASCT. Standard clinical criteria were used to assess for the presence of infection. Result: Seventy-two febrile episodes occurred in 54 of 65 enrolled patients; 29 (40%) of the episodes occurred after neutrophil engraftment. Infections were identified as the cause of 28% and 24% of the neutropenic and post-engraftment febrile episodes, respectively. The level of IL-12 decreased and that of IL-6 increased significantly during fever because of infection, such that the IL-12:IL-6 ratio accurately excluded infection. The area under the ROC curve for the IL-12:IL-6 ratio was 0.88 (95% CI 0.79-0.97). The sensitivity, specificity, positive predictive and negative predictive values associated with a cut-off ratio of 4.1 were 95%, 75%, 60%, and 97%, respectively. Discussion: The IL-12:IL-6 ratio effectively discriminates infectious from non-infectious causes of fever during ASCT. It may be useful in assessing the probability of infection in patients with post-engraftment fever.

Original languageEnglish
Pages (from-to)327-334
Number of pages8
JournalCytotherapy
Volume8
Issue number4
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

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Stem Cell Transplantation
Interleukin-12
Interleukin-6
Fever
Serum
Infection
Neutrophils
Neutropenia
Autologous Transplantation
Hematologic Neoplasms
Interleukin-8
Interleukin-1
ROC Curve
Interleukin-10
Area Under Curve
Interleukin-2
Enzyme-Linked Immunosorbent Assay
Cytokines
Costs and Cost Analysis
Sensitivity and Specificity

Keywords

  • Autologous transplantation
  • Cytokine
  • Fever
  • IL-12
  • IL-6

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Tuma, R. A., Almyroudis, N. G., Sohn, S. J., Panageas, K., Rice, R. D., Galinkin, D., ... Kewalramani, T. (2006). The serum IL-12: IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation. Cytotherapy, 8(4), 327-334. https://doi.org/10.1080/14653240600845237

The serum IL-12 : IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation. / Tuma, R. A.; Almyroudis, N. G.; Sohn, S. J.; Panageas, K.; Rice, R. D.; Galinkin, D.; Blain, M.; Montefusco, M.; Pamer, E. G.; Nimer, Stephen D; Kewalramani, T.

In: Cytotherapy, Vol. 8, No. 4, 01.08.2006, p. 327-334.

Research output: Contribution to journalArticle

Tuma, RA, Almyroudis, NG, Sohn, SJ, Panageas, K, Rice, RD, Galinkin, D, Blain, M, Montefusco, M, Pamer, EG, Nimer, SD & Kewalramani, T 2006, 'The serum IL-12: IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation', Cytotherapy, vol. 8, no. 4, pp. 327-334. https://doi.org/10.1080/14653240600845237
Tuma, R. A. ; Almyroudis, N. G. ; Sohn, S. J. ; Panageas, K. ; Rice, R. D. ; Galinkin, D. ; Blain, M. ; Montefusco, M. ; Pamer, E. G. ; Nimer, Stephen D ; Kewalramani, T. / The serum IL-12 : IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation. In: Cytotherapy. 2006 ; Vol. 8, No. 4. pp. 327-334.
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abstract = "Background: Fever during neutropenia and after neutrophil engraftment (post-engraftment fever) occurs commonly during autologous transplantation (ASCT), but infections are infrequently identified. Tests that reliably exclude infection may reduce the cost and toxicity of unnecessary diagnostic testing and empiric treatment. We assessed whether serum levels of inflammatory cytokines could distinguish infectious from non-infectious causes of fever in patients undergoing ASCT. Methods: Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL- 12(p70), TNF-α and IFN-γ were measured by sandwich ELISA at multiple pre-determined times and at the onset of the first fever during neutropenia and after neutrophil engraftment in patients with hematologic malignancies undergoing ASCT. Standard clinical criteria were used to assess for the presence of infection. Result: Seventy-two febrile episodes occurred in 54 of 65 enrolled patients; 29 (40{\%}) of the episodes occurred after neutrophil engraftment. Infections were identified as the cause of 28{\%} and 24{\%} of the neutropenic and post-engraftment febrile episodes, respectively. The level of IL-12 decreased and that of IL-6 increased significantly during fever because of infection, such that the IL-12:IL-6 ratio accurately excluded infection. The area under the ROC curve for the IL-12:IL-6 ratio was 0.88 (95{\%} CI 0.79-0.97). The sensitivity, specificity, positive predictive and negative predictive values associated with a cut-off ratio of 4.1 were 95{\%}, 75{\%}, 60{\%}, and 97{\%}, respectively. Discussion: The IL-12:IL-6 ratio effectively discriminates infectious from non-infectious causes of fever during ASCT. It may be useful in assessing the probability of infection in patients with post-engraftment fever.",
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T2 - IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation

AU - Tuma, R. A.

AU - Almyroudis, N. G.

AU - Sohn, S. J.

AU - Panageas, K.

AU - Rice, R. D.

AU - Galinkin, D.

AU - Blain, M.

AU - Montefusco, M.

AU - Pamer, E. G.

AU - Nimer, Stephen D

AU - Kewalramani, T.

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N2 - Background: Fever during neutropenia and after neutrophil engraftment (post-engraftment fever) occurs commonly during autologous transplantation (ASCT), but infections are infrequently identified. Tests that reliably exclude infection may reduce the cost and toxicity of unnecessary diagnostic testing and empiric treatment. We assessed whether serum levels of inflammatory cytokines could distinguish infectious from non-infectious causes of fever in patients undergoing ASCT. Methods: Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL- 12(p70), TNF-α and IFN-γ were measured by sandwich ELISA at multiple pre-determined times and at the onset of the first fever during neutropenia and after neutrophil engraftment in patients with hematologic malignancies undergoing ASCT. Standard clinical criteria were used to assess for the presence of infection. Result: Seventy-two febrile episodes occurred in 54 of 65 enrolled patients; 29 (40%) of the episodes occurred after neutrophil engraftment. Infections were identified as the cause of 28% and 24% of the neutropenic and post-engraftment febrile episodes, respectively. The level of IL-12 decreased and that of IL-6 increased significantly during fever because of infection, such that the IL-12:IL-6 ratio accurately excluded infection. The area under the ROC curve for the IL-12:IL-6 ratio was 0.88 (95% CI 0.79-0.97). The sensitivity, specificity, positive predictive and negative predictive values associated with a cut-off ratio of 4.1 were 95%, 75%, 60%, and 97%, respectively. Discussion: The IL-12:IL-6 ratio effectively discriminates infectious from non-infectious causes of fever during ASCT. It may be useful in assessing the probability of infection in patients with post-engraftment fever.

AB - Background: Fever during neutropenia and after neutrophil engraftment (post-engraftment fever) occurs commonly during autologous transplantation (ASCT), but infections are infrequently identified. Tests that reliably exclude infection may reduce the cost and toxicity of unnecessary diagnostic testing and empiric treatment. We assessed whether serum levels of inflammatory cytokines could distinguish infectious from non-infectious causes of fever in patients undergoing ASCT. Methods: Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL- 12(p70), TNF-α and IFN-γ were measured by sandwich ELISA at multiple pre-determined times and at the onset of the first fever during neutropenia and after neutrophil engraftment in patients with hematologic malignancies undergoing ASCT. Standard clinical criteria were used to assess for the presence of infection. Result: Seventy-two febrile episodes occurred in 54 of 65 enrolled patients; 29 (40%) of the episodes occurred after neutrophil engraftment. Infections were identified as the cause of 28% and 24% of the neutropenic and post-engraftment febrile episodes, respectively. The level of IL-12 decreased and that of IL-6 increased significantly during fever because of infection, such that the IL-12:IL-6 ratio accurately excluded infection. The area under the ROC curve for the IL-12:IL-6 ratio was 0.88 (95% CI 0.79-0.97). The sensitivity, specificity, positive predictive and negative predictive values associated with a cut-off ratio of 4.1 were 95%, 75%, 60%, and 97%, respectively. Discussion: The IL-12:IL-6 ratio effectively discriminates infectious from non-infectious causes of fever during ASCT. It may be useful in assessing the probability of infection in patients with post-engraftment fever.

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