Effect of Liposomal and Free Bisphosphonates on the IL-1β, IL-6 and TNFα Secretion from RAW 264 Cells in Vitro
Identifieur interne : 002B66 ( Main/Exploration ); précédent : 002B65; suivant : 002B67Effect of Liposomal and Free Bisphosphonates on the IL-1β, IL-6 and TNFα Secretion from RAW 264 Cells in Vitro
Auteurs : Niina Pennanen [Finlande] ; Seppo Lapinjoki [Finlande] ; Arto Urtti [Finlande] ; Jukka Mönkkönen [Finlande]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 1995-06-01.
English descriptors
Abstract
Abstract: Purpose. In order to evaluate the possible antiinflammatory action of bisphosphonates, the effect of the drugs on the secretion of proinflammatory cytokines (IL-lβ, IL-6 and TNFα) from macrophages was studied. Liposomes or high concentration of extracellular calcium was used to enhance the intracellular delivery of bisphosphonates. Methods. RAW 264 cells were used as macrophage model, and they were induced with lipopolysaccharide to produce the cytokines. The cytokine concentrations in the culture supernatants were measured with time-resolved fluoroimmunoassay. Results. As a free drug, clodronate and pamidronate, but not etidronate, inhibited LPS-stimulated secretion of the cytokines from macrophage-like RAW 264 cells. Low concentrations of pamidronate, however, induced the IL-6 secretion, and the cytokine inhibitory action at the higher concentrations of pamidronate was attributed to cytotoxicity of the compound. The cytokine induction or toxic effects were not observed with clodronate or etidronate. When the drugs were encapsulated in negatively charged unilamellar liposomes, the inhibitory potency of both clodronate and etidronate enhanced by a factor of 10-20, while that of pamidronate was not increased. The complex formation of bisphosphonates with extracellular calcium, although enhancing the uptake of the compounds by macrophages, did not considerably increase their cytokine inhibitory potency. Conclusions. Bisphosphonates have inhibitory action on cytokine secretion by macrophages. The non-cytotoxic cytokine inhibition by liposome encapsulated clodronate could be beneficial in local inflammatory diseases, where the inflammation is sustained by the excessive amounts of inflammatory cytokines produced by activated macrophages.
Url:
DOI: 10.1023/A:1016281608773
Affiliations:
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In order to evaluate the possible antiinflammatory action of bisphosphonates, the effect of the drugs on the secretion of proinflammatory cytokines (IL-lβ, IL-6 and TNFα) from macrophages was studied. Liposomes or high concentration of extracellular calcium was used to enhance the intracellular delivery of bisphosphonates. Methods. RAW 264 cells were used as macrophage model, and they were induced with lipopolysaccharide to produce the cytokines. The cytokine concentrations in the culture supernatants were measured with time-resolved fluoroimmunoassay. Results. As a free drug, clodronate and pamidronate, but not etidronate, inhibited LPS-stimulated secretion of the cytokines from macrophage-like RAW 264 cells. Low concentrations of pamidronate, however, induced the IL-6 secretion, and the cytokine inhibitory action at the higher concentrations of pamidronate was attributed to cytotoxicity of the compound. The cytokine induction or toxic effects were not observed with clodronate or etidronate. When the drugs were encapsulated in negatively charged unilamellar liposomes, the inhibitory potency of both clodronate and etidronate enhanced by a factor of 10-20, while that of pamidronate was not increased. The complex formation of bisphosphonates with extracellular calcium, although enhancing the uptake of the compounds by macrophages, did not considerably increase their cytokine inhibitory potency. Conclusions. Bisphosphonates have inhibitory action on cytokine secretion by macrophages. The non-cytotoxic cytokine inhibition by liposome encapsulated clodronate could be beneficial in local inflammatory diseases, where the inflammation is sustained by the excessive amounts of inflammatory cytokines produced by activated macrophages.</div></front></TEI><affiliations><list><country><li>Finlande</li></country></list><tree><country name="Finlande"><noRegion><name sortKey="Pennanen, Niina" sort="Pennanen, Niina" uniqKey="Pennanen N" first="Niina" last="Pennanen">Niina Pennanen</name></noRegion><name sortKey="Lapinjoki, Seppo" sort="Lapinjoki, Seppo" uniqKey="Lapinjoki S" first="Seppo" last="Lapinjoki">Seppo Lapinjoki</name><name sortKey="Monkkonen, Jukka" sort="Monkkonen, Jukka" uniqKey="Monkkonen J" first="Jukka" last="Mönkkönen">Jukka Mönkkönen</name><name sortKey="Urtti, Arto" sort="Urtti, Arto" uniqKey="Urtti A" first="Arto" last="Urtti">Arto Urtti</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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