Effects of interferon-alpha 2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis

Interferon (IFN)-alpha a known inhibitor of myelopoiesis. is increasingly u sed to treat patients with systemic mastocytosis (SM). However, the mechani sms of IFN-ce effects on mast cell (MC) growth remain unknown, and the trea tment responses may be variable. In the present study, factor-dependent ex vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs ) was analyzed in a patient with SM treated with IFN-alpha 2b (3 million U/ day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to > 1400 ng/ml). PBMNCs were collected before and during IFN-alpha 2b treatment and culture d in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 da ys. In the absence of SCF, no MC growth was detectable. However, in the pre sence of SCF, MC containing tryptase appeared in the cultures. Treatment wi th IFN-a2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-alpha 12b treat ment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-2ab treatment. However after a latency per iod of a few months, tryptase concentrations declined and then reached a pl ateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-alpha 2b . In summary. our data show that IFN-alpha 2b can exhibit inhibitory effect s on factor-dependent growth of MC progenitor cells. However, it still rema ins open which of the patients with mastocytosis can benefit from long-term IFN-alpha treatment.