Interleukin-6 is a potent thrombopoietic factor in vivo in mice

Abstract

To determine the biologic activity of interleukin-6 (IL-6) on megakaryocytopoiesis and thrombocytopoiesis in vivo, the cytokine was administered intraperitoneally to mice every 12 hours at varying doses for five days or for varying time intervals, based on the kinetic analysis of IL-6 serum levels indicating the peak of 40 minutes following injection, with no detection at 150 minutes. A dose-response experiment showed that IL-6 increased platelet counts in a dose- dependent fashion at a plateau stimulation level of 5 micrograms. Administration of 5 micrograms of IL-6 reproducibly elevated platelet counts at five days by approximately 50% to 60% of increase. Moreover, a striking increase in megakaryocytic size in response to IL-6 was elicited by the treatment, but no change in megakaryocyte numbers; whereas IL-6 administration did not expand CFU-MK numbers. The in vivo studies in this manner had negligible effects on other hematologic parameters, with the minor exception of monocyte levels. These data show that IL-6 acts on maturational stages in megakaryocytopoiesis and promotes platelet production in vivo in mice, suggesting that IL-6 functions as thrombopoietin.

Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants

“…Thus, we emphasized the significance of the serial evaluation of thrombopoietic cytokines to determine their roles in secondary thrombocytosis. IL-6 and IL-11 are known to have potential to increase platelet counts in vivo (Ishibashi et al, 1989;Tepler et al, 1996). However, our study showed that IL-6 was not elevated to the levels observed in neonatal infections (Messor et al, 1996), and that there was no significant relationship to thrombocytosis.…”

The megakaryocyte platelet system and vascular disease

“…platelet volume are under independent hormonal control [31]. The proliferation differentiation and maturation of megakaryocytes is regulated by interleukin-3, interleukin-6, thrombopoietin and other colony stimulating factors [32][33][34][35][36][37][38]. Changes in platelet volume may be related to an alteration in the fragmentation pattern of the megakaryocyte either in the pulmonary circulation as suggested by Trowbridge [39] and Martin [40] or by fragmentation ofMK pseudopods in the bone marrow [41].…”

The clinical value of hematological markers in rheumatoid arthritis patients treated with tocilizumab

“…It has been revealed that IL-6 could act on maturational stages in megakaryocytopoiesis and promotes Plt production in vivo in mice, suggesting that IL-6 could function as thrombopoietin. 37 In inflammatory thrombocytosis, IL-6 could induce thrombocytosis through thrombopoietin (TPO). 38 In addition, it has been reported that administration of IL-6 to humans leads to an increase in circulating Plt counts.…”