IN-VIVO INHIBITION OF LOCALIZED BONE-RESORPTION BY HUMAN RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST

Interleukin-1 (IL-1) has been implicated as a primary mediator of bone remodeling; it is a powerful activator of bone resorption both in viv o and in vitro. However, there is no direct evidence that IL-1 plays a role in physiological bone modeling or remodeling. Interleukin-1 rece ptor antagonist (IL-1ra) is a member of the IL-1 family, which bind to IL-1 receptors and blocks the action of IL-1 alpha and IL-1 beta. We have previously shown that IL-1ra blocks IL-1-induced bone resorption in vitro. Evidence is reported here that human recombinant IL-1ra (hrI L-1ra) inhibits strain-induced modeling in the gerbil auditory bulla w hile having no significant effect on apposition rate. Pressurization o f the auditory bulla to 10 mm Hg above atmospheric pressure increased osteoclast surface from 3.62 to 19.14%. Infusion of hrIL-1ra during pr essurization resulted in significant inhibition of osteoclast surface on the pressurized side. These findings suggest that IL-1 is a physiol ogical mediator of bone modeling and that hrIL-1ra inhibits resorption but not apposition in the auditory buna model.