INTERLEUKIN-11 - A NEW CYTOKINE CRITICAL FOR OSTEOCLAST DEVELOPMENT

Stromal cells of the bone marrow control the development of osteoclast s through the production of cytokines capable of promoting the prolife ration and differentiation of hematopoietic progenitors. Moreover, the deregulated production of the cytokine IL-6 in the bone marrow mediat es an increase in osteoclastogenesis after estrogen loss. IL-6, howeve r, does not influence osteoclastogenesis in the estrogen-replete state , suggesting that other cytokines might be responsible for osteoclast development under physiologic circumstances. We report here that IL-11 , a newly discovered cytokine that is produced by marrow stromal cells , induced the formation of osteoclasts exhibiting an unusually high de gree of ploidy in cocultures of murine bone marrow and calvarial cells . Osteoclasts formed in the presence of IL-11 were capable of bone res orption, as evidenced by the formation of resorption pits, as well as the release of Ca-45 from prelabeled murine calvaria. Further, an anti body neutralizing IL-11 suppressed osteoclast development induced by e ither 1,25-dihgdroxyvitamin D-3, parathyroid hormone, interleukin-1, o r tumor necrosis factor; whereas inhibitors of IL-1 or TNF had no effe ct on IL-11-stimulated osteoclast formation. The effects of IL-11 on o steoclast development were blocked by indomethacin; more important, ho wever, they were independent of the estrogen status of the marrow dono rs.