The Serum Cytokine Profiles of Lymphoma-associated Hemophagocytic Syndrome: A Comparative Analysis of B-Cell and T-Cell/Natural Killer Cell Lymphomas

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Abstract
To elucidate the differences in pathogenesis between lymphoma-associated hemophagocytic syndromes (LAHS) of theT-cell/ natural killer cell (T/NK) and B-cell (B) types,we comparatively analyzed the clinical features and serum cytokine profiles of 33 patients with LAHS registered in the Kyoto University Hematology/Oncology Study Group.The serum cytokine levels of each patient group (B-LAHS versusT/NK-LAHS) were expressed as the ratio of the median to the upper normal values of the respective cytokines and were as follows: 19.05 versus 13.99 for soluble interleukin 2 (IL-2) receptor, 0.67 versus 0.67 for granulocytemacrophage colony-stimulating factor (GM-CSF), 0.64 versus 1.26 for G-CSF, 5.70 versus 3.61 for M-CSF, 1.54 versus 3.39 for interferon γ (IFN-γ), 13.17 versus 1.17 for IL-6, 6.88 versus 1.58 for tumor necrosis factor α (TNF-α), 0.71 versus 0.41 for IL-1, 1.99 versus 0.21 for IL-12, and 105.32 versus 29.65 for IL-10.The serum levels of IL-6,TNF-α, and IL-10 were significantly higher in the B-LAHS group,whereas those of IFN-γ were significantly lower. These differences between the 2 groups may reflect a difference in the pathogenesis. Higher serum levels of IL-6, TNF-α, and IL-10 may be derived at least partly from neoplastic B-cells themselves. In addition, the extremely high serum levels of IL-10 suggest that a compensatory anti-inflammatory process may operate in both groups and give rise to a profound immunosuppressive state and a poor outcome.