Effects of Zoledronate on Local and Systemic Production of IL-1 β, IL-18, and TNF-α in Mice and Augmentation by Lipopolysaccharide.

Effects of Zoledronate on Local and Systemic Production of IL-1β, IL-18, and TNF-α in Mice and Augmentation by Lipopolysaccharide.
Biol Pharm Bull. 2019;42(6):929-936
Authors: Funayama H, Tashima I, Okada S, Ogawa T, Yagi H, Tada H, Wakita R, Asada Y, Endo Y
Abstract
Bisphosphonates (BPs) containing nitrogen (N-BPs) exhibit far stronger anti-bone-resorptive effects than non-N-BPs. However, repeated administration of N-BPs causes osteonecrosis selectively in jawbones. As BPs accumulate in large amounts within inflamed bones, any N-BP released from the pool accumulated within jawbones might directly act on cells in the surrounding soft-tissues and induce inflammation or necrosis. Here, we examined the local and systemic effects of zoledronate (the most potent N-BP with the highest incidence of jawbone-necrosis) on inflammatory cytokines in mice. Locally within ear-pinnas: (i) zoledronate induced long-lasting accumulation of interleuikin-1β (IL-1β) and IL-18, but not tumor necrosis factor-α (TNF-α), (ii) zoledronate and lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria) mutually augmented the productions of IL-1β, IL-18, and TNF-α, and (iii) oxidronate (a toxic non-N-BP) by itself produced not only IL-1β and IL-18, but also TNF-α. In systemic experiments using intraperitoneal injection of zoledronate and/or LPS, (i) zoledronate by itself increased none of the above cytokines in serum, and (ii) in mice pr...

Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Funayama H, Tashima I, Okada S, Ogawa T, Yagi H, Tada H, Wakita R, Asada Y, Endo Y Tags: Biol Pharm Bull Source Type: research