Role of Interleukins on Physiological and Pathological Bone Resorption and Bone Formation. II. Effects by Cytokines in the IL-6 and IL-10 Families

Abstract Interleukins make up a large cytokine superfamily, currently consisting of IL-1 to IL-40. Although initially thought to be intercellular signaling molecules important for crosstalk between different leukocytes, interleukins are now known as pleiotropic molecules produces by most cell types, acting mainly as paracrine signals on a wide variety of different target cells. A few interleukins also can act as endocrine molecules. Since the discovery of osteoclast activating factor produced by mononuclear leukocytes and later found to be interleukin-1β, many interleukins have been found to affect bone resorption and bone formation. Interleukins can affect osteoclast differentiation and activity by acting directly on osteoclast progenitors or mature osteoclasts, but several of the interleukins regulate bone resorption indirectly by acting on nearby cells such as osteoblasts, osteocytes, mononuclear leukocytes or synovial fibroblasts. Interleukins regulating bone formation usually do so by acting directly on cells in the osteoblastic lineage. Cytokines can be classified based upon the numeric order of discovery, their functions, their postulated roles as pro- or anti-inflammatory cytokines, cell of origin or based upon common receptor components. In three chapters, effects by the interleukin superfamily on bone cells are discussed, including their effects on physiological remodeling of the skeleton and their suggested roles in inflammation-induced modeling and in metastatic bone disease. The interleukins in these chapters are divided in subfamilies mainly based upon shared receptor components. In the present chapter, effects by interleukins in the IL-6 and IL-10 families are discussed.