Ambivalent role of copper in inflammatory disorders.

Soluble copper (Cu) preparations are both acute/chronic irritants and effective anti-inflammatory agents in rats. Copper is a prevalent component in several folk remedies for arthritis. Patients with rheumatoid arthritis and ankylosing spondylitis are reported to have higher-than-normal levels of serum copper, mainly associated with albumin. The anti-arthritis drug, D-penicillamine (Pn), efficiently strips Cu from some of its (pharmacologically inert) storage forms, e.g. Cu-albumin, Cu-polynucleotides yielding low M.W. Cu-Pn complexes, which show anti-inflammatory activity (ca. 5 X phenylbutazone) in rats irritated with carrageenan, oleyl alcohol, sodium urate and adjuvants. Under certain conditions Pn also blocks the amine-oxidase activity of caeruloplasmin, a circulating copper protein which is elevated in inflamed animals (an 'acute phase reactant'). Drugs, nutritional factors and the disease process may all possibly affect the movement of copper in vivo between inert reversible pharmacoactive reversible toxic forms.