CONTINUOUS-INFUSION OF INTERLEUKIN-6 IN SUBLETHALLY IRRADIATED MICE ACCELERATES PLATELET RECONSTITUTION AND THE RECOVERY OF MYELOID BUT NOTOF MEGAKARYOCYTIC PROGENITOR CELLS IN BONE-MARROW

Interleukin-6 (IL-6) is a pleiotropic cytokine that enhances the matur ation of megakaryocytes. In mice, in vivo treatment with IL-6 results in elevated platelet counts both in untreated animals and after myelos uppressive therapy. In this study, we assessed the effect of continuou s infusion of IL-6 in sublethally irradiated (7 Gy) mice on peripheral blood cell counts and progenitor cells in bone marrow and spleen. Fem ale Swiss mice were treated by continuous infusion with 1 or 10 mu g I L-6 per day for 7 or 14 days. Continuous infusion of IL-6 for 7 days r esulted in elevated levels of circulating IL-6 (mean: 1872 pg/mL vs. 1 00 pg/mL for phosphate-buffered saline [PBS]-treated controls) and in an accelerated reconstitution of platelets starting at day 12 after ir radiation. In IL-6-treated animals, the 50% pretreatment platelet coun t was reached on day 15 vs. day 21 for irradiated controls receiving n o IL-6. Treatment with IL-6 for 14 days resulted in a further increase in platelet counts, exceeding the pretreatment counts. The number of colony-forming units-megakaryocyte (CFU-Mk) was significantly elevated from day 6 to 18 in the spleen but not in bone marrow. To assess the contribution of extramedullary megakaryocytopoiesis in the spleen to I L-6-induced platelet recovery, IL-6 was also administered to splenecto mized mice. The stimulatory effect of IL-6 on platelet recovery was pr eserved in these animals, indicating that megakaryocytopoiesis in the spleen did not contribute to the accelerated recovery of platelets. Th e neutrophil counts were elevated during IL-6 treatment and became sim ilar to controls after cessation of therapy, whereas the numbers of co lony-forming units-granulocyte/macrophage (CFU-GM) in the bone marrow were elevated from day 9 to 24 in all animals treated with 10 mu g IL- 6 per day. In conclusion, continuous infusion of IL-6 stimulates plate let recovery after irradiation without increasing the number of CFU-MB and conversely stimulates the proliferation of myeloid progenitor cel ls without an effect on neutrophil reconstitution.