Inflammatory cytokines in virus-associated hemophagocytic syndrome: Interferon-gamma as a sensitive indicator of disease activity

Shouichi Ohga, Akinobu Matsuzaki, Mari Nishizaki, Takako Nagashima, Takeshi Kai, Masahiro Suda, Kohji Ueda

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Abstract

Purpose: We assayed serum interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels in children with virus-associated hemophagocytic syndrome (VAHS) to evaluate the relationship of these cytokines to other laboratory parameters. We also studied the role of IFN-γ as a macrophage activator in hemophagocytic syndrome (HPS). Patients and Methods: Interleukin-1 beta, TNF-α, and IFN-γ were measured in 42 serial sera from six children with VAHS using a sensitive radioimmunoassay. Results: The cytokine IFN-γ or TNF was detected in 19/ 19 (100%) or 11/19 (69%) samples, respectively, during the active febrile phase, at much higher levels than during the remission phase of the disease (IFN: p < 0.00001; TNF: p < 0.01). In contrast, IL-1 could be detected in only two sera obtained from a patient during severe relapse. Serial cytokine examination revealed that the elevated TNF and IFN-γ levels decreased rapidly to an undetectable level in concert with clinical improvement after an effective treatment, and that IFN-γ, but not TNF, was detected just before a relapse marked by spiking fever. In the active phase, the CD4/8 ratio was depressed, and the total number of CD3+ HLA-DR+ cells was increased. of the activated T cells, CD8+ cells outnumbered CD4+ T cells. By the Spearman’s rank sum test, the IFN-7 level correlated positively with the peripheral leukocyte count [Correlation coefficient (CC): 0.585, p < 0.05] and serum lactate dehydrogenase level (CC: 0.538, p < 0.05) and negatively with the CD4/8 ratio (CC: −0.618, p < 0.05), but not with any other parameter including ferritin and C-reactive protein. Although TNF and IL-1 were not statistically linked to these parameters, TNF levels were related to IFN-γ levels (product moment CC: 0.546, p < 0.05). Conclusions: These results suggest that circulating IFN-γ is one of the most sensitive indicators of disease activity; it may act as a potent macrophage activator during the hypercytokinemic state of childhood VAHS.

Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalAmerican Journal of Pediatric Hematology/Oncology
Volume15
Issue number3
Publication statusPublished - Aug 1993
Externally publishedYes

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Hemophagocytic Lymphohistiocytosis
Interleukin-1beta
Interferon-gamma
Cytokines
Viruses
Serum
Fever
Macrophages
T-Lymphocytes
Recurrence
HLA-DR Antigens
Ferritins
Nonparametric Statistics
Leukocyte Count
L-Lactate Dehydrogenase
Interferon-alpha
C-Reactive Protein
Radioimmunoassay
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Inflammatory cytokines in virus-associated hemophagocytic syndrome : Interferon-gamma as a sensitive indicator of disease activity. / Ohga, Shouichi; Matsuzaki, Akinobu; Nishizaki, Mari; Nagashima, Takako; Kai, Takeshi; Suda, Masahiro; Ueda, Kohji.

In: American Journal of Pediatric Hematology/Oncology, Vol. 15, No. 3, 08.1993, p. 291-298.

Research output: Contribution to journalArticle

Ohga, Shouichi ; Matsuzaki, Akinobu ; Nishizaki, Mari ; Nagashima, Takako ; Kai, Takeshi ; Suda, Masahiro ; Ueda, Kohji. / Inflammatory cytokines in virus-associated hemophagocytic syndrome : Interferon-gamma as a sensitive indicator of disease activity. In: American Journal of Pediatric Hematology/Oncology. 1993 ; Vol. 15, No. 3. pp. 291-298.
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abstract = "Purpose: We assayed serum interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels in children with virus-associated hemophagocytic syndrome (VAHS) to evaluate the relationship of these cytokines to other laboratory parameters. We also studied the role of IFN-γ as a macrophage activator in hemophagocytic syndrome (HPS). Patients and Methods: Interleukin-1 beta, TNF-α, and IFN-γ were measured in 42 serial sera from six children with VAHS using a sensitive radioimmunoassay. Results: The cytokine IFN-γ or TNF was detected in 19/ 19 (100{\%}) or 11/19 (69{\%}) samples, respectively, during the active febrile phase, at much higher levels than during the remission phase of the disease (IFN: p < 0.00001; TNF: p < 0.01). In contrast, IL-1 could be detected in only two sera obtained from a patient during severe relapse. Serial cytokine examination revealed that the elevated TNF and IFN-γ levels decreased rapidly to an undetectable level in concert with clinical improvement after an effective treatment, and that IFN-γ, but not TNF, was detected just before a relapse marked by spiking fever. In the active phase, the CD4/8 ratio was depressed, and the total number of CD3+ HLA-DR+ cells was increased. of the activated T cells, CD8+ cells outnumbered CD4+ T cells. By the Spearman’s rank sum test, the IFN-7 level correlated positively with the peripheral leukocyte count [Correlation coefficient (CC): 0.585, p < 0.05] and serum lactate dehydrogenase level (CC: 0.538, p < 0.05) and negatively with the CD4/8 ratio (CC: −0.618, p < 0.05), but not with any other parameter including ferritin and C-reactive protein. Although TNF and IL-1 were not statistically linked to these parameters, TNF levels were related to IFN-γ levels (product moment CC: 0.546, p < 0.05). Conclusions: These results suggest that circulating IFN-γ is one of the most sensitive indicators of disease activity; it may act as a potent macrophage activator during the hypercytokinemic state of childhood VAHS.",
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AU - Nishizaki, Mari

AU - Nagashima, Takako

AU - Kai, Takeshi

AU - Suda, Masahiro

AU - Ueda, Kohji

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N2 - Purpose: We assayed serum interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels in children with virus-associated hemophagocytic syndrome (VAHS) to evaluate the relationship of these cytokines to other laboratory parameters. We also studied the role of IFN-γ as a macrophage activator in hemophagocytic syndrome (HPS). Patients and Methods: Interleukin-1 beta, TNF-α, and IFN-γ were measured in 42 serial sera from six children with VAHS using a sensitive radioimmunoassay. Results: The cytokine IFN-γ or TNF was detected in 19/ 19 (100%) or 11/19 (69%) samples, respectively, during the active febrile phase, at much higher levels than during the remission phase of the disease (IFN: p < 0.00001; TNF: p < 0.01). In contrast, IL-1 could be detected in only two sera obtained from a patient during severe relapse. Serial cytokine examination revealed that the elevated TNF and IFN-γ levels decreased rapidly to an undetectable level in concert with clinical improvement after an effective treatment, and that IFN-γ, but not TNF, was detected just before a relapse marked by spiking fever. In the active phase, the CD4/8 ratio was depressed, and the total number of CD3+ HLA-DR+ cells was increased. of the activated T cells, CD8+ cells outnumbered CD4+ T cells. By the Spearman’s rank sum test, the IFN-7 level correlated positively with the peripheral leukocyte count [Correlation coefficient (CC): 0.585, p < 0.05] and serum lactate dehydrogenase level (CC: 0.538, p < 0.05) and negatively with the CD4/8 ratio (CC: −0.618, p < 0.05), but not with any other parameter including ferritin and C-reactive protein. Although TNF and IL-1 were not statistically linked to these parameters, TNF levels were related to IFN-γ levels (product moment CC: 0.546, p < 0.05). Conclusions: These results suggest that circulating IFN-γ is one of the most sensitive indicators of disease activity; it may act as a potent macrophage activator during the hypercytokinemic state of childhood VAHS.

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