TY - JOUR
T1 - Cutting edge
T2 - Nitrogen bisphosphonate-induced inflammation is dependent upon mast cells and IL-1
AU - Norton, John T.
AU - Hayashi, Tomoko
AU - Crain, Brian
AU - Cho, John S.
AU - Miller, Lloyd S.
AU - Corr, Maripat
AU - Carson, Dennis A.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84859377311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859377311&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1100830
DO - 10.4049/jimmunol.1100830
M3 - Article
C2 - 22387558
AN - SCOPUS:84859377311
SN - 0022-1767
VL - 188
SP - 2977
EP - 2980
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -