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Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic
lymphohistiocytosis
Y Osugi, J Hara, S Tagawa, K Takai, G Hosoi, Y Matsuda, H Ohta, H Fujisaki, M Kobayashi, N Sakata, K Kawa-Ha, S Okada and A Tawa
Department of Pediatrics, Osaka University Hospital, Suita, Japan.
Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation
of T cells and macrophages. The clinical characteristics associated with
this disease result from overproduction of Th1 cytokines including
interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis
factor-alpha (TNF-alpha). In this study, we analyzed the production of
IL-12 and IL-4, which determine Th1 and Th2 response, respectively, and
IL-10, which antagonizes Th1 cytokines, in 11 patients with HLH. IL-12 was
detected in plasma in all patients (mean peak value, 30.0 +/- 5.0 pg/mL),
while IFN-gamma was massively produced in nine patients (mean peak value,
79.2 +/- 112.0 U/mL). IL-4 was not detected in any of the patients. Plasma
IL-10 levels were elevated in all patients (mean peak value, 2,698.0 +/-
3,535.0 pg/mL). There was a positive correlation between the levels of
IFN-gamma and IL- 10 (P < .01). The plasma concentrations of these
cytokines were initially high, before decreasing after the acute phase.
However, the decrease in IL-10 levels was slower than that of IFN-gamma.
Although the concentration of IL-12 was high at the acute phase, in some
patients, a peak in the level was delayed until the chronic phase. Thus, in
HLH, production of cytokines that promote development of Th1 cells appears
to be predominant over that for Th2 cell development. Overproduction of
IL-10 was also observed indicating that a mechanism suppressing
hyperactivation of Th1 cells and monocytes/macrophages functions in
patients with this disease.
Volume 89,
Issue 11,
pp. 4100-4103,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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