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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shibazaki, M. Sugawara, S. Takada, H. Kosugi, H. Endo, Y. |
| Description | Author Affiliation: Sugawara S ( Department of Microbiology & Immunology, School of Dentistry, Tohoku University, Sendai, Japan.) |
| Abstract | 1. Aminobisphosphonates (aminoBPs), potent inhibitors of bone resorption, have been reported to induce inflammatory reactions such as fever and an increase in acute phase proteins in human patients, and to induce the histamine-forming enzyme, histidine decarboxylase, in mice. In the present study, we examined the effect of aminoBP, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP), on the production of the pro-inflammatory cytokines, IL-1 and TNFalpha, in mice. 2. Intraperitoneal injection of AHBuBP did not itself produce detectable levels of IL-1 (alpha and beta) and TNFalpha in the serum. However, the elevation of serum IL-1 induced by lipopolysaccharide (LPS) was greatly augmented in mice injected with AHBuBP 3 days before the LPS injection, whereas the LPS-induced elevation of serum TNFalpha was almost completely abolished. 3. Spleen and bone marrow cells taken from mice injected with AHBuBP produced IL-1beta in vitro spontaneously, and the production was augmented following the addition of LPS. Cells that accumulated in the peritoneal cavity in response to AHBuBP produced a particularly large amount of IL-1beta. However, AHBuBP treatment of mice did not lead to an impairment of the in vitro production of TNFalpha by these three types of cells. 4. Liposomes encapsulating dichloromethylene bisphosphonate (a non-amino BP) selectively deplete phagocytic macrophages. When an intraperitoneal injection of these liposomes was given 2 days after an injection of AHBuBP, there was a marked decrease in the LPS-induced elevation of serum IL-1 (alpha and beta) (LPS being injected 3 days after the injection of AHBuBP). 5. These results indicate that AHBuBP has contrasting effects on the in vivo LPS-induced production of IL-1 and TNFalpha in mice, enhancing the production of IL-1 by phagocytic macrophages and suppressing the production of TNFalpha, although underling mechanisms remain to be clarified. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 125 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Alendronate Pharmacology Interleukin-1 Metabolism Tumor Necrosis Factor-alpha Animals Bone Marrow Cells, Cultured Lipopolysaccharides Liposomes Macrophages Drug Effects Mice Mice, Inbred BALB C Phagocytosis Spleen Time Factors Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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