CYTOKINE PRODUCTION REGULATING TH1 AND TH2 CYTOKINES IN HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivat ion of T cells and macrophages. The clinical characteristics associate d with this disease result from overproduction of Th1 cytokines includ ing interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necr osis factor-alpha (TNF-alpha). In this study, we analyzed the producti on of IL-12 and IL-4, which determine Th1 and Th2 response, respective ly, and IL-10, which antagonizes Th1 cytokines, in 11 patients with HL H. 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 patien ts (mean peak value, 79.2 +/- 112.0 U/mL). IL-4 was not detected in an y of the patients. Plasma IL-10 levels were elevated in ail patients ( mean peak value, 2,698.0 +/- 3,535.0 pg/mL). There was a positive corr elation between the levels of IFN-gamma and IL-10 (P < .01). The plasm a concentrations of these cytokines were initially high, before decrea sing 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 de layed until the chronic phase. Thus, in HLH, production of cytokines t hat promote development of Th1 cells appears to be predominant over th at 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. (C) 1997 by The American Society of Hematology.