Interleukin-11: a new cytokine critical for osteoclast development.

Abstract

Stromal cells of the bone marrow control the development of osteoclasts through the production of cytokines capable of pro- moting the proliferation and differentiation of hematopoietic progenitors.Moreover, the deregulated production of the cyto- kine IL-6 in the bone marrow mediates an increase in osteoclastogenesis after estrogen loss.IL-6, however, does not influence osteoclastogenesis in the estrogen-replete state, suggesting that other cytokines might be responsible for osteoclast devel- opment under physiologic circumstances.We report here that IL-1l, a newly discovered cytokine that is produced by marrow stromal cells, induced the formation of osteoclasts exhibiting an unusually high degree of ploidy in cocultures of murine bone marrow and calvarial cells.Osteoclasts formed in the presence of IL-il were capable of bone resorption, as evidenced by the formation of resorption pits, as well as the release of 'Ca from prelabeled murine calvaria.Further, an antibody neutralizing IL-1l suppressed osteoclast development induced by either 1,25-dihydroxyvitamin D3, parathyroid hormone, interleukin- 1, or tumor necrosis factor; whereas inhibitors of IL-1 or TNF had no effect on IL-li-stimulated osteoclast formation.The effects of IL-1l on osteoclast development were blocked by indomethacin; more important, however, they were independent of the estrogen status of the marrow donors.(J.Clin.Invest.1994.93:1516-1524.)Key words: 1,25-dihydroxyvitamin D3 * parathyroid hormone * interleukin-l * tumor necrosis factor * interleukin-6 kines such as IL-6 seems to mediate an increase in osteoclasto- genesis in certain states of pathologic bone resorption, includ- ing estrogen deficiency (6-9).Indeed, we had previously dem- onstrated that ovariectomy in mice causes an increase in the number of colony-forming units for granulocytes and macro- phages (CFU-GM),' the presumed osteoclast precursors in the