THE ANTIINFLAMMATORY ACTIVITY OF METAL-COMPLEXES AND SALTS OF AMINE CARBOXYBORANES

The metal complexes and salts of amine carboxyboranes were shown to be potent anti-inflammatory agents in rodents at 8 mg kg-1. They were ef fective in blocking induced edema, pleurisy and endotoxic shock while blocking both local and central pain processes. The ability of the age nts to function as anti-inflammatory agents is multi-fold. First, lyso somal enzymes of specific cells, e.g. macrophages, were inhibited with IC50 values in the range of 10(-6) M. Collagenase I and II activities were inhibited with IC50 values approximately equal to 10(-4) M. The anti-inflammatory activity of these agents at the molecular levels app ears to be due to inhibition of the release of TNFalpha and Il-1 from macrophages which indirectly control chemotaxic migration of white blo od cells as indicated by the suppression of PMN and macrophage invasio n into sponges implanted subcutaneously (SC) in mice. Furthermore, in these invading cells, the agents' blockage of TNFalpha and Il-1 or Il- 2 release down-regulates prostaglandin and leukotriene enzymatic synth etic rates and, consequently, their release, resulting in a reduction of the inflammation process.