Abstract
The amine-carboxyboranes and related derivatives have been shown to be
potent anti-inflammatory and anti-osteoporosis agents. Their action in
part appears to be mediated by the modulation of cytokines, e.g. TNFα
or IL-1. Previous studies have demonstrated that LPS induced
macrophages release of TNFα maximally at 60 to 90 min. and IL-1 from 5
to 8 hr. The amine-carboxyboranes reduced significantly the release of
these cytokines but also blocked TNFα high affinity binding to UMR-106
receptor at 90 min. at 10 μM, and IL-1 high affinity binding at 5 hr. at
12.5 μM. In addition, the agents suppressed IL-8 binding to CHO K1 high
affinity receptor at 24 hr. at 50 μM and IL-2 binding to HuT-8 receptors
at 25 μM at 90 min. and 5 hr. Correlation of metabolic events
associated with osteoporosis showed that at 90 min., when TNFα receptor
binding was reduced by the agents, calcium uptake into UMR-106 cells was
reduced at 10 μM as well as the acid and alkaline phosphatases, and the
prostaglandin cyclo-oxygenase activities and adhesion of leukocytes and
macrophages to UMR-106 cell monolayers. At 5hr. when the agents reduced
IL-1 binding to UMR-106 receptors, calcitonin and 1,25-dihydrovitamin