PURPOSE: We assayed serum interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) 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-gamma as a macrophage activator in hemophagocytic syndrome (HPS). PATIENTS AND METHODS: Interleukin-1 beta, TNF-alpha, and IFN-gamma were measured in 42 serial sera from six children with VAHS using a sensitive radioimmunoassay. RESULTS: The cytokine IFN-gamma 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-gamma levels decreased rapidly to an undetectable level in concert with clinical improvement after an effective treatment, and that IFN-gamma, 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-gamma 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-gamma levels (product moment CC: 0.546, p < 0.05). CONCLUSIONS: These results suggest that circulating IFN-gamma 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.
PURPOSE: We assayed serum interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) 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-gamma as a macrophage activator in hemophagocytic syndrome (HPS). PATIENTS AND METHODS: Interleukin-1 beta, TNF-alpha, and IFN-gamma were measured in 42 serial sera from six children with VAHS using a sensitive radioimmunoassay. RESULTS: The cytokine IFN-gamma 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-gamma levels decreased rapidly to an undetectable level in concert with clinical improvement after an effective treatment, and that IFN-gamma, 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-gamma 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-gamma levels (product moment CC: 0.546, p < 0.05). CONCLUSIONS: These results suggest that circulating IFN-gamma 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.
Authors: Naval Daver; Kenneth McClain; Carl E Allen; Sameer A Parikh; Zaher Otrock; Cristhiam Rojas-Hernandez; Boris Blechacz; Sa Wang; Milen Minkov; Michael B Jordan; Paul La Rosée; Hagop M Kantarjian Journal: Cancer Date: 2017-06-16 Impact factor: 6.860
Authors: R H F Vivan; P C Leonello; L A Nagashima; M S Kaminami; F S M Tristão; A Sano; M A Ono; C V Béjar; E N Itano Journal: Mycopathologia Date: 2009-11-08 Impact factor: 2.574