Clodronate (dichloromethylene bisphosphonate) inhibits LPS-stimulated IL-6 and TNF production by raw 264 cells |
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| Institution: | 1. Department of Pharmaceutical Technology and A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland;2. Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland;1. Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania;2. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania;3. Department of Surgery, VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, Pennsylvania;4. Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania;1. School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, PR China;2. School of Medical Devices, Shenyang Pharmaceutical University, Benxi, Liaoning Province 117004, PR China;1. Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;2. Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;1. Department of Intensive Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;2. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;3. Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;1. Department of Environmental Science, Indira Gandhi National Tribal University, Amarkantak, MP-484887, India;2. Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi, India;3. Department of Botany, Banaras Hindu University, Varanasi, 221005, India;4. State Government Forest Department, Kolhapur, Maharashtra, India |
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| Abstract: | Effect of liposome-encapsulated and free clodronate on the IL-6 and TNF production by macrophages was studied using RAW 264 cell line as a macrophage model, and dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) for analysis of secreted cytokines. LPS-stimulated RAW 264 cells proved to produce notable amounts of these two cytokines, and DELFIA was sensitive and reliable method for analysis. Liposome-encapsulated clodronate inhibited the production of both cytokines, IL-6 being affected more than TNF, and the effect was mostly due to the drug itself, not to liposomal lipid. More than ten times higher concentration of free clodronate than liposomal clodronate was needed to inhibit cytokine production. This is the first report on the cytokine inhibitory property of clodronate, and the results support the idea of the use of liposomal clodronate as a macrophage suppressive agent in autoimmune diseases. |
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