Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis.
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.
Osugi
Y
Y
Department of Pediatrics, Osaka University Hospital, Suita, Japan.
Hara
J
J
Tagawa
S
S
Takai
K
K
Hosoi
G
G
Matsuda
Y
Y
Ohta
H
H
Fujisaki
H
H
Kobayashi
M
M
Sakata
N
N
Kawa-Ha
K
K
Okada
S
S
Tawa
A
A
D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000097:blood / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines