Possible role of macrophage‐colony stimulating factor in the development of hemophagocytic syndrome 1

To the Editor: The pathogenesis of reactive hemophagocytic syndrome is still poorly understood. Since this syndrome is often seen following infection in individuals predisposed by existing immunosuppression, abnormality in the immune regulatory pathway is considered to be related to the mechanism responsible for the intense hemophagocytic activity of the reactive macrophages (1,2). Recent studies suggested the implication of cytokines released from activated T cells in the syndrome (3). To establish which cytokines are responsible for the development of this syndrome we measured the levels of several cytokines which could stimulate or be released from the macrophages in the serum of 7 patients with typical virus-associated-hemophagocytic syndrome. The results showed a prominent increase in the macrophage-colony stimulating factor (M-CSF) levels (enzyme-linked immunosorbent assay, ELISA, Green-Cross Co. Ltd., Osaka) in all 7 cases (Table 1). Similarly, an increase in the tumor necrosis factor-a (TNF-a) levels (ELISA, BML Co. Ltd., Tokyo) was observed in all 5 cases examined (Table 1). On the other hand, levels of interferon-y (IFN-y ), granulocyte-macrophage-CSF (GM-CSF), interleukin-1P (IL-1p) and IL-6 were all normal and that of granulocyte-CSF (G-CSF) varied with the cases (ELISA, BML) (4). Reiner et al. reported the involvement of IFN-y, TNF and IL-1 in bone marrow suppression and that of IFN-y and GM-CSF in macrophage activation in patients with this syndrome (2). Amongst other factors, excessive production of IFN-y from uncontrolled T cells is considered to play a central role, by acting on a variety of cells with a resulting cytokine cascade with GM-CSF and IL-6 mediating macrophage activation and tissue damage (5) . Our observations would not rule out the above possibility since serum cytokine levels may not necessarily reflect their local levels. However, we strongly suggest that M-CSF and TNF-a play a crucial role in the major feature of the syndrome, activation and proliferation of macrophages. As these cytokines not only actint of