Cutting edge: Nitrogen bisphosphonate-induced inflammation is dependent upon mast cells and IL-1

John T. Norton, Tomoko Hayashi, Brian Crain, John S. Cho, Lloyd S. Miller, Maripat Corr, Dennis A. Carson

Research output: Contribution to journalArticlepeer-review

Abstract

Nitrogen-containing bisphosphonates (NBPs) are taken by millions for bone disorders but may cause serious inflammatory reactions. In this study, we used a murine peritonitis model to characterize the inflammatory mechanisms of these agents. At dosages comparable to those used in humans, injection of NBPs into the peritoneum caused recruitment of neutrophils, followed by an influx of monocytes. These cellular changes corresponded to an initial increase in IL-1α, which preceded a rise in multiple other proinflammatory cytokines. IL-1R, IL-1α, and IL-1β were required for neutrophil recruitment, whereas other MyD88-dependent signaling pathways were needed for the monocyte influx. Mice deficient in mast cells, but not mice lacking lymphocytes, were resistant to NBP-induced inflammation, and reconstitution of these mice with mast cells restored sensitivity to NBPs. These results document the critical role of mast cells and IL-1 in NBP-mediated inflammatory reactions.

Original languageEnglish (US)
Pages (from-to)2977-2980
Number of pages4
JournalJournal of Immunology
Volume188
Issue number7
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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