In vivo and in vitro inhibitory effect of α-interferon on megakaryocyte colony growth in essential thrombocythaemia

Megakaryocyte (MK) colony growth of bone marrow mononuclear non-adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK-colony forming units (CFU-MK per 3 x 105 plated cells) was similar in ET (68 ± 33) and in controls (63 ± 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P<0.01) greater in ET patients. Human recombinant α-interferon 2a (α-IFN), administered to 10 patients at a dose of 3 x 106 IU/d s.c. for 11 ± 3 weeks, was capable of inducing a significant (P<0.01) decrease in the number (from 72 ± 16 to 31 ± 14) and size of bone marrow CFU-MK, together with a significant reduction of the platelet count (from 1031 ± 325 to 378 ± 75 x 109/l). When added in vitro at time 0 to the culture dishes, α-IFN inhibited the CFU-MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that α-IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented anti-proliferative effect of this cytokine.