Copper-dependent antioxidase defenses in inflammatory and autoimmune rheumatic diseases.
Gel-filtered sera of patients with various inflammatory and autoimmune rheumatic diseases (N = 354) were screened for the presence of the inflammation marker Cu-thionein. The concentrations of Cu-thionein were significantly diminished in patients with connective tissue diseases (P < 0.001). Sera of patients suffering from inflammatory rheumatic diseases were almost totally depleted of this low-molecular-weight copper protein that exerts pronounced superoxide dismutase activity and scavenges effectively hydroxyl radicals and singlet oxygen. Cortisone treatment of patients with rheumatoid arthritis, systemic lupus erythematosus, and polymyalgia rheumatica replenished impressively the serum concentration of Cu-thionein. The partial oxidation of the EPR-silent Cu(I)-chromophore to Cu(II)/Cu(I)-thionein, which is essential for the catalytic dismutation of superoxide, was monitored by electron paramagnetic resonance in the presence of activated neutrophils and monocytes. Release of Cu-thionein during the oxidative burst of peripheral blood monocytes was demonstrated in vitro. The role of prooxidant-antioxidant imbalances in the pathogenesis of rheumatic diseases is discussed.
Miesel
R
R
Deutsches Rheumaforschungszentrum, Berlin, Germany.
Zuber
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D002850:Chromatography, Gel; D003240:Connective Tissue Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D003300:Copper / Q000502:physiology*; D003348:Cortisone / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007388:Internal Medicine; D008668:Metallothionein / Q000097:blood* / Q000172:deficiency; D009369:Neoplasms / Q000097:blood; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000378:metabolism; D012216:Rheumatic Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology
C007121:copper thionein; D003300:Copper; D008668:Metallothionein; D003348:Cortisone