The role of IL-1β in the bone loss during rheumatic diseases

Abstract

Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin- (IL-) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL-1β in the pathogenesis of bone loss. Furthermore, we analysed the role of IL-1β in bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti-IL-1β therapy in this field.

Figure 1

The inflammatory cascade during autoimmune and autoinflammatory diseases leading to bone resorption. Activated T cells produce IL-1β and RANKL. IL-1β stimulates T and B cells in an autocrine and paracrine fashion amplifying the inflammatory response. Macrophages after influence of IL1 and RANKL produce these 2 molecules and transdifferentiate toward preosteoclasts, which activated themselves, display strong homing to the bone, and produced higher levels of IL-1β and RANKL leading to the increased bone resorption.