An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates.

摘要: We studied the acute phase response, including specific cytokine production, [interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor α(TNFα)] following a single dose of Aredia (disodium pamidronate) in patients with increased bone turnover and, vitro, role played by cytokines acute-phase reaction which may follow administration aminobisphosphonates. An vivo exploratory study was done on 24 in- and outpatients given intravenous pamidronate 60 mg. Measurements were taken at baseline 24, 48, 72 hours. The main outcome measures changes from serum IL-1, IL-6, TNFα. In addition, C-reactive protein (CRP), white blood cell count (WCC), lymphocyte count, elastase concentration measured. Symptomatic evaluation made fever, pain, rigors. whole eight healthy volunteers exposed to various concentrations three bisphosphonates—pamidronate, clodronate, zoledronate. immediately before 3, 6, 10 hours after exposure drugs. vivo, there statistically significant (P < 0.001) increase median values TNFα all post-baseline measurements. Median for IL-6 also showed dosing. There no IL-1 values. Few any change total WCC or but 62.5% normal range CRP above levels treatment. Fourteen experienced fever; 2 reported correlation between fever cytokines. serious adverse experiences premature discontinuations due poor tolerability, 91% expressed willingness receive again. an mild seen bisphosphonates, greatest effects highest both No observed agent. Significant within 3 days treated first time confirming previous findings. However, lack vitro does not support hypothesis that this plays major reaction. cellular mechanism interaction among aminobisphosphonates, Il-6, requires further investigations. results are consistent