metallothionein and Rheumatic-Diseases

Sera of patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of xanthine oxidase (XOD) and compared to sera from healthy donors and patients with nonrheumatic diseases including AIDS, internal diseases, and different carcinomas. Up to 50-fold higher levels of XOD were detected in rheumatic sera (P < 0.001). In addition, serum sulfhydryls (SH) were determined as sensitive markers of oxidative stress. The SH status in rheumatic patients was diminished by 45-75% (P < 0.001) and inversely correlated to the concentration of serum XOD (R = 0.73), suggesting a causal interrelation. The depletion of serum sulfhydryls by the oxyradical-producing XOD/acetaldehyde system was mimicked successfully ex vivo in human serum from healthy donors. Cortisone treatment of patients suffering from systemic lupus erythematosus and rheumatoid arthritis impressively normalized elevated XOD concentrations in rheumatic sera to those of healthy controls. The participation of xanthine oxidase in the depletion of serum antioxidants in rheumatic patients is discussed in the light of substrate availability and Km values.

Topics: Acetaldehyde; Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Biomarkers; Cohort Studies; Cortisone; Female; Humans; Inflammation; Internal Medicine; Male; Metallothionein; Neoplasms; Organometallic Compounds; Oxidation-Reduction; Oxygen; Rheumatic Diseases; Schiff Bases; Singlet Oxygen; Stress, Physiological; Sulfhydryl Compounds; Xanthine Oxidase

Sera from 354 patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of reactive nitrogen intermediates, antinuclear antibodies and the anti-oxidase copper-thionein (Cu-thionein), and compared to sera from healthy donors and patients with non-rheumatic diseases including AIDS, various internal as well as neurological diseases and carcinoma of different organs. When compared to healthy individuals, the levels of nitric oxides in sera from patients with autoimmune rheumatic diseases were elevated by 240-600% (P < 0.01). The status of reactive nitrogen intermediates (NOx, RNI) in sera from donors with inflammatory rheumatic diseases was increased by 170-540%, but was also significantly enhanced in sera of patients with non-rheumatic diseases, indicating a general inflammatory mechanism that is predominantly triggered by inducible nitric oxide (NO) syntheses of phagocytes. All rheumatic sera were dramatically depleted of the anti-oxidase Cu-thionein (P < 0.001), a powerful consumer of hydroxyl radicals and singlet oxygen and an efficient superoxide dismutase. The NOx levels were positively correlated with the serum titers of antinuclear antibodies (r = 0.77) and negatively correlated with Cu-thionein levels (r = 0.94), reflecting a high steady-state concentration of free radicals generated during inflammatory and autoimmune rheumatic diseases.

Topics: Antibodies, Antinuclear; Humans; Metallothionein; Nitrogen Oxides; Rheumatic Diseases; Severity of Illness Index

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.

Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Chromatography, Gel; Connective Tissue Diseases; Copper; Cortisone; Humans; Inflammation; Internal Medicine; Metallothionein; Neoplasms; Oxidation-Reduction; Phagocytes; Rheumatic Diseases