Alendronate augments interleukin-1 beta release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

作者：Deng Xue; Tamai Riyoko; Endo Yasuo; Kiyoura Yusuke^*

来源：Toxicology and Applied Pharmacology, 2009, 235(1): 97-104.

DOI：10.1016/j.taap.2008.11.005

• Bisphosphonates (BPs)
• Porphyromonas gingivalis
• Tannerella forsythia
• Interleukin-1 beta (IL-1 beta)
• Tumor necrosis factor alpha (TNF alpha)
• Alendronate
• Clodronate
• Pam(3)CSK(4)
• Lipid A
• Caspase-1

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1 beta, but not TNF alpha, production by macrophages infected with P gingivalis or T. forsythia. This augmentation of IL-1 beta production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1 beta production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1 beta induced by alendronate and P gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1 beta release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.

• 出版日期2009-2-15