Neuron-specific enolase in hemophagocytic lymphohistiocytosis: A potentialindicator for macrophage activation?

To determine the pathogenesis of hemophagocytic lymphohistiocytosis (HLH), serum levels of neuron-specific enolase (NSE) and cytokine profiles were in vestigated. Serum concentrations of NSE and several cytokines were measured by immunoassays, and the association was evaluated in 18 HLH patients. Ser um NSE levels increased (>10 ng/mL) in 27/29 samples (93%) during the activ e febrile phase, the mean level of which (35.9 ng/mL) was much higher than that during the remission phase (11.2 ng/mL) (P = .001). The peak levels of NSE in 11 patients who required cytotoxic agents were higher than those in 7 patients without chemotherapy, 64.6 +/- 49.4 and 17.9 +/- 12.9, respecti vely (P = .265). The NSE levels correlated positively with the levels of in terferon (IFN)-gamma (Pearson's correlation coefficient [r] = 0.408, P = .0 44), soluble interleukin-2 receptor (sIL-2R) (r = 0.464, P = .048), lactate dehydrogenase (r = 0.830, P <.00001), aspartate aminotransferase (r = 0.53 1, P = .003), acid ferritin (r = 0.715, P = .00001), and correlated negativ ely with platelet count (r = -0.422, P = .021), but not with other paramete rs, including tumor necrosis factor-alpha, IL-1 beta, IL-18, soluble Fas li gand and C-reactive protein. Multiple regression analysis indicated that th e correlation of NSE with platelet count was independent of other correlati ons. Sequential NSE changes well reflected the clinical course of patients. Immunohistochemical staining revealed an appreciable number of NSE-positiv e histiocytes in bone marrow specimens with florid hemophagocytosis. These results suggest that the circulating NSE originated from macrophages stimul ated with IFN-gamma/sIL-2R, and partly from the destruction of platelets. S erum NSE level may be a useful marker for predicting the disease progressio n of HLH. Int J Hematol. 2000;72:55-60. (C) 2000 The Japanese Society of He matology.