Is copper pro- or anti-inflammatory? A reconciling view and a novel approach for the use of copper in the control of inflammation.

The anti-inflammatory role of copper is well-known although still largely unexplained. On the other hand, the capacity of copper to induce the formation of damaging .OH radicals in vivo is no longer debated. These two aspects of the physiological activity of copper have been considered to be paradoxical. Arguments developed here show that they may actually derive from a single chemical process, the type of physiological effect observed depending on the ligand bound to the copper ions involved in Fenton chemistry. Both iron and copper are Fenton catalysts. Given its intrinsic coordination properties, however, copper induces more site-specific .OH damage to the ligands bound to it. It, therefore, appears that copper complexes with specific .OH-inactivating ligands (OILs) can be used as "lures" for the Fenton reaction, .OH radicals preferentially formed on these being immediately inactivated. The hypothesis is thus put forward here that copper-OIL complexes acting as effective Fenton catalysts are potential "catalase-like" anti-inflammatory drugs.