BONE-MARROW NEUTROPHILIA AND SUPPRESSED BONE TURNOVER IN HUMAN INTERLEUKIN-6 TRANSGENIC MICE - A CELLULAR RELATIONSHIP AMONG HEMATOPOIETIC-CELLS, OSTEOBLASTS, AND OSTEOCLASTS MEDIATED BY STROMAL CELLS IN BONE-MARROW

To elucidate the effect of interleukin-6 (IL-6) on bone and bone marro w (BM), human IL-6 transgenic mice (hIL-6 tgm) were produced. Their bo ne and BM were examined histologically, radiologically, histomorphomet rically, and hematologically on a temporal basis. hIL-6 tgm showed his tologically evident neutrophilia in BM. Increase in precursors of gran ulocytes and monocytes in hIL-6 tgm was demonstrated by an assay for c olony forming unit in culture (CFU-C) of BM cells. Decrease in osteobl asts and osteoid and suppression of primary spongiosa formation were p redominantly observed in hIL-6 tgm at 14 weeks old, the terminal stage of life for hIL-6 tgm. An assay for colony forming unit in fibroblast ic (CFU-F) of BM cells revealed a decrease in osteoblast precursor (wi th regard to alkaline phosphatase-positive colonies) in hIL-6 tgm at 1 5 weeks old. Histomorphometry demonstrated a decrease of both osteocla st number and bone resorption in hIL-6 tgm. These results suggested th at enhanced granulocytic hematopoiesis, suppressed bone turnover, and alteration of cellular population in stromal cells in BM occurred in h IL-6 tgm. Thus we provide new findings that facilitate understanding o f cellular interrelationships among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in BM.