In vivo and in vitro inhibitory effect of alpha-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 10(5) 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 less than 0.01) greater in ET patients. Human recombinant alpha-interferon 2a (alpha-IFN), administered to 10 patients at a dose of 3 x 10(6) IU/d s.c. for 11 +/- 3 weeks, was capable of inducing a significant (P less than 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 10(9)/l). When added in vitro at time 0 to the culture dishes, alpha-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 alpha-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 antiproliferative effect of this cytokine.
Gugliotta
L
L
Institute of Haematology L.e A. Seràgnoli, University of Bologna, Italy.
Bagnara
G P
GP
Catani
L
L
Gaggioli
L
L
Guarini
A
A
Zauli
G
G
Belmonte
M M
MM
Lauria
F
F
Macchi
S
S
Tura
S
S
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D003114:Colony-Forming Units Assay; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects*; D008875:Middle Aged; D011994:Recombinant Proteins; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000473:pathology*
D007370:Interferon Type I; D011994:Recombinant Proteins