IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release.
IL-6 enhances the differentiation of pluripotent hematopoietic stem cells but predominantly affects the differentiation of hematopoietic cells in the granulocyte-macrophage lineage. We have previously shown that multinucleated cells (MNC) with many features of the osteoclast phenotype form in long term human marrow cultures. Addition of rhIL-6 (10 to 100 pg/ml) to these cultures significantly increased MNC formation, with greater than 80% of the MNC expressing an Ag that cross-reacts with the mAb 23c6. This antibody preferentially binds to osteoclasts. rhIL-6 did not enhance MNC formation in marrow cultures treated with 1,25 dihydroxyvitamin D3, a potent stimulator of MNC formation, but significantly increased the percentage of MNC that cross-reacted with the 23c6 mAb. Addition of antihuman IL-1 to cultures treated with rhIL-6 totally inhibited the increase in MNC formation stimulated by rhIL-6. In contrast, anti-IL-1 did not affect MNC formation stimulated by 1,25 dihydroxyvitamin D3. Further, conditioned media from marrow cultures exposed to rhIL-6 contained elevated levels of IL-1 beta (500 pg/ml compared to 23 pg/ml in control cultures 15 h after IL-6 addition). These results suggest that the capacity of rhIL-6 to stimulate formation of MNC which cross-react with 23c6 is mediated by induction of release of IL-1 beta.
Kurihara
N
N
Research Service, Audie Murphy VA Hospital, San Antonio, TX 78284.
Bertolini
D
D
Suda
T
T
Akiyama
Y
Y
Roodman
G D
GD
D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D002116:Calcitonin / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism* / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology*; D011994:Recombinant Proteins; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D002116:Calcitonin