Comparative Effects of Thrombopoietin and Interleukin-6 on Murine Megakaryocytopoiesis and Platelet Production

A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) derived from human embryonic kidney (HEK) cells is known to increase platelet production and to increase the number of morphologically unrecognizable early megakaryocytes, ie, small acetylcholinesterase-positive (SAChE+) cells in mice. Other recent studies have concluded that interleukin-6 (IL-6) also stimulates murine megakaryocytopoiesis both in vitro and in vivo. Some workers have suggested that IL-6 is thrombopoietin. Therefore, the purpose of this study was to compare the effects of TSF and IL-6 on percent 35S incorporation into platelets, platelet sizes, and the percentages of SAChE+ cells in C3H mice, and to determine if they produce the same or different responses. The results showed that two or four injections of a partially purified TSF (total dose of 2 or 4 units (U) over a 1- or 2-day period) increased percent 35S incorporation into platelets (P < .005) and platelet sizes (P < .005) of both normal and rebound-thrombocytotic mice when compared with values from other mice treated with human serum albumin, the carrier protein for both TSF and IL-6. In eight separate experiments, it was shown that IL-6 (40,000 U, 4 pg), when given to reboundthrombocytotic mice in four injections over a 2-day period, produced a small but significant (P < .005) increase in percent 35S incorporation into platelets. Additional studies showed that negative results were obtained when similar high doses of IL-6 were administered in two doses over a 1-day period. TSF, but not IL-6, stimulated an increase in platelet sizes of normal mice (P < .005 to 0.0005); however, IL-6 increased platelet sizes of rebound-thrombocytotic mice when given in two or four injections (P < .05 to .0005). Also, IL-6, but not TSF, caused anemia in normal mice (P < .0005) that were given two injections and tested 3 days later. TSF stimulated an increase (P < .005) in the percentage of SAChE+ cells; whereas IL-6, even at high doses, did not. Because of the observed differences in biologic responses of these two cytokines, we conclude that TSF and IL-6 are separate entities.