Production of interleukin 3 and granulocyte-macrophage colony-stimulating factor from stimulated blood mononuclear cells in patients with aplastic anemia.

Blood cells from patients with aplastic anemia (AA) were evaluated for the ability to produce interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on stimulation with phytohemagglutinin (PHA) or antilymphocyte globulin (ALG) by the use of an IL-3-dependent cell-line, TF-1, and the GM-CSF-IRMA kit. The IL-3 levels in patients with active AA were significantly lower, both in PHA-stimulated conditioned medium (CM) and in ALG-CM, than those of normal healthy donors (HD; p < 0.01). The degree of reduced IL-3 production in AA patients correlated well with the severity of neutropenia; the level of IL-3 returned to normal after successful treatment with ALG plus methylprednisolone (ALG therapy). On the other hand, GM-CSF production in AA patients varied widely and was only significant in remission patients in PHA-CM; in this case production was higher than that in active AA patients (p < 0.05) or in HD (p < 0.01). Sensitivity to PHA or ALG stimulation was evaluated by the ratio of IL-3 concentrations in ALG-CM versus PHA-CM (ALG/PHA index). The index varied widely from < 0.1 to > 10 in AA patients, contrasting to the clustered values in HD. Seven of the eight patients who had an ALG/PHA index of > 1.0 showed a good clinical response to ALG therapy. However, 12 of the 14 patients who had a lower index (< 1.0) failed to respond. The ALG/PHA index might have an ability to predict the response to ALG therapy.